Treatment tip with protected electrodes

ABSTRACT

Described herein are treatment tip apparatuses (e.g., devices, systems, etc.) including one, or more preferably a plurality, of electrodes that are protected by an electrode partition, such as an electrode housing (which may be retractable) until pressed against the tissue for deployment of the electrodes and delivery of a therapeutic treatment. In particular, these apparatuses may include a plurality of treatment electrodes (e.g., needle electrodes) and be configured for the delivery of nanosecond pulsed electric fields.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/247,469, filed Jan. 14, 2019, titled “TREATMENT TIP WITH PROTECTEDELECTRODES”, which application claims the benefit of priority to U.S.Provisional Patent Application No. 62/618,022, filed Jan. 16, 2018,titled “TREATMENT TIP WITH PROTECTED NEEDLES”, both of which are hereinincorporated by reference in their entirety.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference in their entirety to the sameextent as if each individual publication or patent application wasspecifically and individually indicated to be incorporated by reference.

FIELD

Described herein are electrical applicators that may be preferentiallyused to apply high voltage, ultra-short electrical pulses to treatpatients. Specifically, described herein are retractable treatment tipapparatuses and methods of using them for high-voltage nanosecond pulseelectrical therapy.

BACKGROUND

Ultra-short, high-field strength electric pulses have been described forelectroperturbation of biological cells. For example, electric pulsesmay be used in treatment of human cells and tissue including tumorcells, such as basal cell carcinoma, squamous cell carcinoma, andmelanoma. The voltage induced across a cell membrane may depend on thepulse length and pulse amplitude. Pulses longer than about 1 microsecondmay charge the outer cell membrane and lead to opening of pores, eithertemporarily or permanently. Permanent openings may result in instant ornear instant cell death. Pulses shorter than about 1 microsecond mayaffect the cell interior without adversely or permanently affecting theouter cell membrane, and result in a delayed cell death with intact cellmembranes. Such shorter pulses with a field strength varying in therange of 10 kV/cm to 100 kV/cm may trigger apoptosis (i.e., programmedcell death) in some or all of the cells exposed to the described fieldstrength and pulse duration. These higher electric field strengths andshorter electric pulses may be useful in manipulating intracellularstructures, such as nuclei and mitochondria.

Nanosecond high voltage pulse generators have been proposed forbiological and medical applications. For example, see: Gundersen et al.“Nanosecond Pulse Generator Using a Fast Recovery Diode”, IEEE 26thPower Modulator Conference, 2004, pages 603-606; Tang et al.“Solid-State High Voltage Nanosecond Pulse Generator,” IEEE Pulsed PowerConference, 2005, pages 1199-1202; Tang et al. “Diode Opening SwitchBased Nanosecond High Voltage Pulse Generators for Biological andMedical Applications”, IEEE Transactions on Dielectrics and ElectricalInsulation, Vol. 14, No. 4, 2007, pages 878-883; Yampolsky et al.,“Repetitive Power Pulse Generator With Fast Rising Pulse” U.S. Pat. No.6,831,377; Schoenbach et al. “Method and Apparatus for IntracellularElectro-Manipulation”, U.S. Pat. No. 6,326,177; Gundersen et al.,“Method for Intracellular Modifications Within Living Cells Using PulsedElectric Fields”, U.S. Patent Application No. 2006/0062074; Kuthi etal., “High Voltage Nanosecond Pulse Generator Using Fast Recovery Diodesfor Cell Electro-Manipulation”, U.S. Pat. No. 7,767,433; Krishnaswamy etal., “Compact Subnanosecond High Voltage Pulse Generation System forCell Electro-Manipulation”, U.S. Patent Application No. 2008/0231337;and Sanders et al., “Nanosecond Pulse Generator”, U.S. PatentApplication No. 2010/0038971. The entire content of these publicationsis incorporated herein by reference.

Because of the extremely high therapeutic voltages, as well as the veryfast pulse times, applicators for delivery of such nanopulse stimulationdevices must be configured so as to avoid arcing between theapplicators. In some cases, the applicator may be configured topenetrate into the tissue for application, and may include multipleneedle-type electrodes. Such applicators may be particularly difficultto use with high-voltage systems while avoiding dangerous arcing. Insome variations, the applicator may require the use of an nonconductivematerial, such as a non-conductive gel, between the patient's tissue andthe applicator. The methods and apparatuses described and illustratedherein may address the issues discussed above.

SUMMARY OF THE DISCLOSURE

Described herein are apparatuses (e.g., devices and systems, includingtreatment tip applicators) and methods for the treatment of tissue thatmay more effectively apply therapeutic energy, including but not limitedto ultra-short, high field strength electric pulses, while avoiding therisk of arcing or otherwise harming the tissue. These applicators may beparticularly well suited, for example, for treatments of variousdiseases, skin disorders, and abnormal tissue growth.

In particular, the apparatuses described herein may be configured assingle-use treatment tips that can be used with a variety of differentreusable generator systems, as will be described in greater detailherein.

The methods and apparatuses described herein include treatment tipshaving a portion of the distal tip region that may be retracted. Any ofthese apparatuses may include an electrode partition, which may beconfigured as a housing, to protect and/or insulate a plurality oftreatment electrodes through which high-voltage rapidly pulsed energymay be delivered into the tissue. These apparatuses may address variousissues with existing treatment tips. In particular, these apparatusesmay be configured safely and reliably to deliver nanopulse electrictreatment. Nanopulse electric treatment may be referred to as nanosecondpulsed electric field (nsPEF) stimulation and may include an electricfield with a sub-microsecond pulse width of between 0.1 nanoseconds (ns)and 1000 nanoseconds, or shorter, such as 1 picosecond. It is sometimesreferred to as sub-microsecond pulsed electric field. NsPEFs often havehigh peak voltages, such as 10 kilovolts per centimeter (kV/cm), 20kV/cm, to 500 kV/cm. Treatment of biological cells with nsPEF technologyoften uses a multitude of periodic pulses at a frequency ranging from0.1 per second (Hz) to 10,000 Hz. NsPEFs have been found to triggerapoptosis, for example, in the diseased tissue or abnormal growth, suchas cancerous or benign tumors. Selective treatment of such tumors withnsPEFs can induce apoptosis within the tumor cells without substantiallyaffecting normal cells in the surrounding tissue due to its non-thermalnature. An example of nsPEF applied to biological cells is shown anddescribed in U.S. Pat. No. 6,326,177 (to Schoenbach et al.), which isincorporated herein by reference in its entirety for all purposes. Thereexists a need for electrodes to deliver nsPEF pulses generated by apulse generator to subjects with minimal distortion and with maximumutility and safety. A subject may be a patient (human or non-human,including animals). A user may operate the apparatuses described hereinon a subject. The user may be a physician (doctor, surgeon, etc.),medical technician, nurse, or care provider.

For example, described herein are treatment tip devices for delivery ofelectrical therapy. Any of the treatment tip devices described hereinmay include: a treatment tip housing; an electrode partition extendingfrom a distal end of the treatment tip housing, wherein the electrodepartition is configured to retract proximally into the treatment tiphousing; and a plurality of treatment electrodes, comprising a firstelectrode and a second electrode, wherein a distal tip of the firstelectrodes and a distal tip of the second electrode are exposed distallybeyond the electrode partition in a deployed configuration when theelectrode partition is driven against a subject's tissue, wherein thedistal tip of the first electrode is separated from the distal tip ofthe second electrode by the electrode partition in an un-deployedconfiguration prior to driving the electrode partition against thesubject's tissue.

As mentioned, the electrode partition may be configured to partially orcompletely cover all or some of the plurality of electrodes when in theun-deployed state. The electrode partition may therefore be referred toherein as an electrode housing; in some variations the electrodepartition does not enclose the electrodes but separates (e.g.,partitions) electrodes in the plurality of electrodes from each other,including electrically isolating them, particularly when applied againsta tissue. This may prevent or reduce arcing, and may prevent accidentinjury, and/or may guide the electrodes, particularly needle electrodes,during insertion into the tissue.

Thus, unless the context makes it clear otherwise, any of the electrodepartitions described herein may be referred to as an electrode housing,and an electrode housing may refer to an electrode partition that atleast partially encloses all or some of the electrodes of the pluralityof electrodes. For example, an electrode partition may comprise anelectrode housing and the plurality of treatment electrodes may at leastpartially be housed within the electrode partition when the device is inthe un-deployed configuration. Either the electrode partition or theelectrode housing may include lateral openings that expose at least partof the one or more electrodes of the plurality of electrodes.

For example, the electrode housing may comprise one or more lateralcut-out regions (e.g., openings, windows, etc.) configured so that atleast part of a lateral side of one or more of the electrodes from theplurality of electrodes are visible in the un-deployed configuration.

As mentioned, in some variations, the treatment tip includes anelectrode partition configured as an electrode housing. The electrodehousing may completely enclose all or some of the plurality ofelectrodes in the un-deployed configuration, or it may partially encloseall or some of the plurality of electrodes in the un-deployedconfiguration (e.g., the electrode housing may be open at the distal endface and/or open along one or more, or part of one or more, sides.

According to some implementations, a treatment tip device for deliveryof electrical therapy may include: a treatment tip housing; an electrodehousing extending from a distal end of the treatment tip housing; and aplurality of treatment electrodes at least partially within theelectrode housing, wherein the device has an un-deployed configurationin which distal ends of the plurality of treatment electrodes do notextend beyond a distal end face of the electrode housing and a deployedconfiguration in which the plurality of treatment electrodes extendbeyond the distal end face of the electrode housing, wherein theelectrode housing and treatment electrodes are configured to moverelative to each other to convert between the un-deployed and thedeployed configurations.

According to further implementations, for example, a treatment tipdevice for delivery of electrical therapy comprises: a treatment tiphousing; an electrode housing extending from a distal end of thetreatment tip housing and configured to retract proximally into thetreatment tip housing; a plurality of treatment electrodes at leastpartially within the electrode housing, wherein the device has anun-deployed configuration in which distal ends of the plurality oftreatment electrodes do not extend beyond a distal end face of theelectrode housing and a deployed configuration in which the electrodehousing is retracted proximally so that the distal ends of the pluralityof treatment electrodes extend beyond the distal end face of theelectrode housing; and a bias opposing retracting the electrode housingfrom the un-deployed configuration to the deployed configuration.

It is further provided a treatment tip device for delivery of electricaltherapy, the device comprising: a treatment tip housing having aplurality of electrical connectors; an electrode housing extending froma distal end of the treatment tip housing, wherein a distal end face ofthe electrode housing comprises a soft and electrically insulatingmaterial and wherein the electrode housing is configured to retractproximally into the treatment tip housing in a deployed configuration; aplurality of treatment electrodes comprising a first needle electrodeand a second needle electrode wherein a distal end of the first needleelectrode is separated from a distal end of the second needle electrodeby the electrode housing in an un-deployed configuration, furtherwherein the plurality of treatment electrodes is in electricalcommunication with the plurality of electrical connectors; wherein thedevice converts between the un-deployed configuration, in which thedistal ends of the plurality of treatment electrodes do not extendbeyond a distal end face of the electrode housing, and the deployedconfiguration in which the electrode housing is retracted proximally sothat the distal ends of the plurality of treatment electrodes extendbeyond the distal end face of the electrode housing.

Any of the treatment tip devices described herein may include a biasthat prevents or limits the conversion between the un-deployed anddeployed configuration. As used herein, a bias generally includes anymechanical resistance element that my limit or prevent the movement ofthe electrode partition or electrode housing relative to the pluralityof electrodes, typically from an un-deployed to a deployedconfiguration, until an appropriate threshold force is applied. In somevariation the bias may provide a return force (e.g., spring force orbias force) tending to return the electrode partition or electrodehousing back to the un-deployed configuration. In some variations thebias may be a release element that prevents movement of the electrodepartition or electrode housing relative to the plurality of electrodesuntil the threshold is exceeded, after which the release disengages,allowing deployment from the un-deployed configuration. For example, abias may comprise one or more of the following: a mechanical resistor, aspring, a detent, a catch, a piston, a mechanical dampener, acompressible material, a release, a friction release, a deflectablerelease, frangible release, and a frictional coupling. The thresholdforce may be any appropriate threshold force and may typically be lowenough to permit a user to, by hand, deploy the device by manuallypushing against the tissue. For example, the threshold force may bebetween 0.01 pounds and 10 pounds of force, e.g., the threshold may be0.01 pounds of force, 0.03 pounds of force, 0.05 pounds of force, 0.07pounds of force, 0.1 pounds of force, 0.12 pounds of force, 0.15 poundsof force, 0.2 pounds of force, 0.3 pounds of force, 0.5 pounds of force,1 pound of force, 1.5 pounds of force, 2 pounds of force, 5 pounds offorce, etc.). In general, any appropriate bias may be used, e.g., tobias the electrode partition in the un-deployed configuration. Asmentioned, the bias may be a mechanical bias, such as a spring (e.g.,coil spring, leaf spring, etc.), an electrical or electromagnetic bias(e.g., a solenoid, etc.), a pneumatic bias, or the like. The bias may bewithin the treatment tip housing and/or within the electrode partition.The bias may apply force between the treatment tip housing and theelectrode partition; in some variations the bias may instead or inaddition apply force between the treatment tip housing and the pluralityof therapeutic electrodes.

Thus, any of the devices described herein may include a bias exerting abias force to oppose conversion from the un-deployed to the deployedconfiguration or from the deployed to un-deployed configuration. Thebias may be overcome by applying a force of greater than the thresholdforce. The bias may be coupled or part of the treatment tip housing, theelectrode partition (e.g., electrode housing), and/or the plurality ofelectrodes.

The bias may be configured to return the electrode housing distally tothe un-deployed configuration with a bias return force. For example, theplurality of treatment electrodes may be extended distally from theelectrode housing when the electrode housing is driven against asubject's tissue with a force exceeding threshold force (which, invariations having a return as part of the bias may be equivalent to thebias return force). The bias may be configured to drive the plurality oftreatment electrodes distally with a bias force. In some variations thebias may include a release lock preventing the electrode partition(e.g., electrode housing) from driving the plurality of treatmentelectrodes distally until the release lock is released.

In general, a treatment electrode may be any appropriate number and/orgroups of electrode. For example, the plurality of treatment electrodesmay comprises a first one or more treatment electrodes and a second oneor more treatment electrodes separated from each other by the electrodehousing. In some variations groups (subsets) of electrodes are groupedtogether and, though separately contacting the skin, may be linkedelectrically to the same source (e.g., anode, cathode, ground, etc.).

As mentioned above, the electrode housing may comprise at least onelateral cut-out (e.g., window) and the first one or more treatmentelectrodes may be positioned to be at least partially visible throughthe at least one lateral cut out. For example, at least one cut-out mayextend along a portion of the length or the full length of the electrodehousing.

All or a portion (e.g., the distal end) of the electrode partition mayinclude an electrical insulator. This electrical insulator may beintegral to the electrode partition distal end (e.g., distal-facing endor tissue-facing end), or it may be a cover or sleeve. For example, theelectrode partition may be formed at least in part of the insulatingmaterial, or the insulating material may be added to other materialforming the electrode partition. The electrode partition may also bereferred to herein as a needle housing or a needle electrode partition.

In general, the electrical insulator may comprise a soft, insulatingmaterial having a durometer of 60 or less on the Shore A hardness scale.For example, the electrical insulator may comprise one or more of:silicon, santoprene, or other TPE (Thermoplastic Elastomer) materials.In any of the apparatuses (e.g., treatment tip devices) described hereinmay include a soft and/or insulated distal end face region of theelectrode partition or electrode housing. For example least the distalend of the electrode housing comprises an electrical insulator. Theelectrical insulator may comprise a soft, insulating material having adurometer of 60 or less on the Shore A hardness scale. The electricalinsulator comprises one or more of: silicon, santoprene, or other TPE(Thermoplastic Elastomer) materials. In some variations, the electricalinsulator comprises an electrically insulating cover.

Any of these apparatuses may include one or more vacuum ports on thedistal end (e.g., through the distal electrically insulating cover). Thevacuum ports may apply suction to hold the distal electricallyinsulating end against the tissue when applying the treatment. Thevacuum ports may couple to one or more vacuum lines within the treatmenttip housing and/or electrode partition and may couple to a vacuum line(e.g., through the reusable handle). In any of the apparatuses describedherein, the handle may be referred to as a headpiece. For example, anyof these devices may include a vacuum port through the electrode housing(e.g., through the electrically insulating cover).

In general, the electrode partition (e.g., electrode housing) isconfigured to retract and extend into the treatment tip housing.However, in some variations, the plurality of treatment electrodes maybe configured to retract and extend into the electrode housing.

In any of the apparatuses described herein, the treatment tip housingmay include a proximal coupling region configured to couple to anapplicator and wherein the proximal coupling region of the treatment tiphousing comprises a plurality of electrical connectors that are inelectrical communication with the plurality of treatment electrodes.Also, in any of the devices described herein, the distal-to-proximallength of the plurality of treatment electrodes may be adjustable.

In general, although the electrodes described herein are shown primarilyas needle electrodes, it should be understood that any of theseelectrodes may be any other type of electrode, such as, e.g., plateelectrodes, probe electrodes, knife electrodes, or the like. Theelectrodes may be configured to penetrate tissue (e.g., having a sharp,pointed, beveled, or otherwise cutting or penetrating end or edge) orthey may be non-penetrating electrodes (e.g., rounded, etc.). Asmentioned, any of the treatment electrodes may comprise treatment needleelectrodes. Needle electrodes may include elongate metal electrodes thatmay have pointed, tissue-penetrating distal ends. In any of thesevariations, the electrode housing may include a needle guide configuredto guide the needle electrodes. Needle guides may be channels that holdthe needle in an orientation (e.g., perpendicular to the distal face ofthe electrode housing) and may help keep the electrode(s) from bendingor curving as they enter the tissue, e.g., as the electrode housing isretracted. An electrode housing including or configured as a needleguide may include one or more openings (channels) that prevent theneedle from bending or curving as it enters the tissue. For example, anelectrode housing may include a tube or channel having an inner diameterthat is approximately the same dimensions (or slightly larger) than theouter dimension of the needle electrodes, allowing it to pass throughthe channel, perpendicular to the face of the electrode housing, andinto the tissue without bending or curving. For example, a needle guidemay be within the electrode housing/partition and configured to guidethe plurality of treatment electrodes as the electrode partition isdeployed when the electrode partition is driven against a subject'stissue. Thus, any of the apparatuses described herein may include aguide (e.g., electrode guide or needle guide) within and/or adjacent tothe electrode partition that is configured to guide the electrodes asthe electrode partition extends and retracts over them and into/out ofthe treatment tip housing. For example, the electrode guide (or multipleelectrode guides may provide a channel or passage that prevents theelectrode from bending or curving when inserting into the tissue. Thismay be particularly helpful with long treatment needle electrodes. Aguide (e.g., needle guide) may be a cylinder or other shaped channelthrough which the electrodes pass when the electrode partition isretracted or extended over the treatment electrodes.

Any of the devices described herein may include one or more fiducialmarker on the electrode partition (e.g., electrode housing) and/or acover for an electrode housing. The fiducial maker may include one ormore fiducial line on the electrode housing. The fiducial marker mayinclude one or more fiducial lines in alignment with one or more rows oftreatment electrodes of the plurality of treatment electrodes, whereinthe fiducial lines identify a location and orientation of the one ormore rows of the plurality of treatment electrodes (e.g., within thehousing in the un-deployed configuration). For example, any of theseapparatus may include one or more fiducial markers or markings on theouter surface of the retractable electrode partition. For example, theapparatus may include a fiducial line (or a plurality of lines) on theelectrode partition. These markings may be labeled (e.g., withalphanumeric characters and/or colors and/or patterns). Fiducialmarkings may be aligned with the therapeutic electrodes (e.g., rows ofneedle electrodes) to help the users align and place the treatment tipin the proper location on the lesion or treatment area.

Any of the devices described herein may include a stop limiting aproximal distance that the electrode housing/partition may be driven inthe deployed configuration. The stop may be adjustable to change thedistance that the electrode housing/partition may be driven in thedeployed configuration. The stop may be, for example, a mechanical stopwithin the tip housing that limits the proximal distance that theelectrode partition may be driven (retracted) when applying the forceexceeding the threshold force that may be set by the bias (e.g., in somevariations may be equivalent to a bias return force). The mechanicalstop may include a rim, ridge, or boss, and may be within the housing.The stop may be adjustable (e.g., using a control on the treatment tiphousing and/or handle). The stop may be adjustable to change theproximal distance that the electrode partition may be driven whenapplying the force exceeding the threshold force.

Also described herein are insulating covers for a needle electrodes(including any of the needle electrodes described above). The insulatingcover may include: a soft body configured to fit over a distal end of ahousing for a needle electrode, wherein the soft body comprises anelectrically insulating material having a durometer of 60 or less on theShore A hardness scale; and a channel through the soft body configuredto pass the needle electrode.

The soft body may comprise a raised ring around the channel. In somevariations, the raised ring forms a gasket. The soft body may comprise adurometer of 45 or less. Any of these insulting covers may include aplurality of channels through the soft body.

As mentioned above, a treatment tip device for delivery of electricaltherapy may include: a treatment tip housing; an electrode partitionextending from a distal end of the treatment tip housing; a plurality oftreatment electrodes comprising a first one or more treatment electrodesand a second one or more treatment electrodes, wherein the device has anun-deployed configuration in which the distal ends of the first one ormore treatment electrodes are separated from the distal ends of thesecond one or more treatment electrodes by the electrode partition, anda deployed configuration in which the plurality of treatment electrodesextend distally beyond the electrode partition, further wherein theelectrode partition and treatment electrodes are configured to moverelative to each other to convert between the un-deployed and thedeployed configurations; and a bias within the treatment tip housingexerting a force to oppose conversion from the un-deployed to thedeployed configuration or from the deployed to un-deployedconfiguration.

Any of the retractable treatment tip devices for delivery of electricaltherapy may include: a treatment tip housing; an electrode partitionextending from a distal end of the treatment tip housing, wherein theelectrode partition is configured to retract proximally into thetreatment tip housing; a bias driving the electrode partition distallywith a bias return force; and a plurality of treatment electrodes,comprising a first electrode and a second electrode, wherein a distaltip of the first electrodes and a distal tip of the second electrode areexposed distally beyond the electrode partition when the electrodepartition is driven against a subject's tissue with a force exceedingthe threshold force to overcome the bias, and wherein otherwise thedistal tip of the first electrode is separated from the distal tip ofthe second electrode by the electrode partition.

For example, a retractable treatment tip device for delivery ofelectrical therapy may include: a treatment tip housing; an electrodepartition extending from a distal end of the treatment tip housing,wherein the electrode partition is configured to retract proximally intothe treatment tip housing, further wherein a distal end face of theelectrode partition comprises an electrical insulator; a bias holdingand/or driving the electrode partition distally with a bias returnforce; and a plurality of treatment electrodes within the electrodepartition; and wherein the plurality of treatment electrodes is exposedbeyond the electrical insulator when the electrode partition is drivenagainst a subject's tissue with a force exceeding a threshold forcesufficient to overcome the bias.

In some variations, a retractable treatment tip device for delivery ofelectrical therapy includes: a treatment tip housing having a proximalcoupling region comprising a plurality of electrical connectors; anelectrode partition extending from a distal end of the treatment tiphousing, wherein the electrode partition is configured to retractproximally into the treatment tip housing; a plurality of treatmentneedle electrodes comprising a first electrodes and a second electrodewherein the first electrode is separated from the second electrode bythe electrode partition, further wherein the plurality of treatmentneedle electrodes are in electrical communication with the plurality ofelectrical connectors; and a bias within the treatment tip housingholding or driving the electrode partition distally with a bias returnforce so that a distal tip of the first electrode is separated from adistal tip of the second electrode by the electrode partition; a distalelectrically insulating cover on a distal end of the electrodepartition, wherein the distal electrically insulating cover comprises asoft material, further wherein the plurality of treatment needleelectrodes extend distally beyond the distal electrically insulatingcover when the electrode partition is driven against a subject's tissuewith a force exceeding the threshold force so that the electrodepartition is driven proximally relative to the plurality of treatmentneedle electrodes.

The treatment tip housing may be configured as a rigid, semi-rigidand/or semi-compliant region into which the electrode partition and/orelectrodes may be at least partially retracted. The treatment tiphousing may be configured to electrically connect the one or moreelectrodes with a controller and/or power source. Any of the treatmenttip housings described herein may be configured as a handle or mayconnect to a handle. The treatment tip housing may be made of, e.g., apolymeric material (e.g., plastic) and may be sterilized. The device,including the treatment tip housing, may be reusable, multiple-useand/or disposable.

In some variations, the electrode partition may be configured as ahousing that at least partially encloses the treatment electrodes. Forexample, described herein are treatment tip devices for delivery ofelectrical therapy (e.g., high-voltage nanosecond pulse electricaltherapy) that include: a treatment tip housing; an electrode partitionextending from a distal end of the treatment tip housing; a plurality oftreatment needle electrodes within the electrode partition, wherein thedevice has an un-deployed configuration in which the distal ends of thetreatment needle electrodes are within the electrode partition and adeployed configuration in which the plurality of treatment needleelectrodes extend through the electrode partition, further wherein theelectrode partition and treatment needle electrodes are configured tomove relative to each other to convert between the un-deployed and thedeployed configurations; and a bias within the treatment tip housingopposing conversion from the un-deployed to the deployed configurationuntil a force exceeding a threshold force is applied.

In some examples the plurality of treatment electrodes (e.g., treatmentneedle electrodes, or electrode plates, etc.) is configured to retractand extend into the treatment tip housing and/or the electrodepartition. For example, the bias may be configured to drive theplurality of treatment electrodes distally once a force greater than athreshold force (e.g., greater than a bias return force when the bias isa spring) is applied. In some variations, the device may furthercomprise a release lock preventing the bias from driving the pluralityof treatment electrodes distally until the release lock is released.

Alternatively or in addition, the electrode partition may be configuredto retract and extend into the treatment tip at least partially (e.g.,by at least 10%, by at least 20%, by at least 30%, by at least 40%, byat least 50%, by at least 60%, by at least 70%, by at least 80%, by atleast 90%, by 100% of the extended length of the electrode partition,)within the treatment tip housing. For example, the bias (or a secondbias) may be configured to drive the electrode partition distally with abias return force, wherein the plurality of treatment electrodes isexposed distal to the electrode partition when the electrode partitionis driven against a subject's tissue with a force exceeding thethreshold force (which may be set by any included bias). In somevariations, the electrode may be driven through and/or out of theelectrode partition.

For example, described herein are retractable treatment tip devices fordelivery of electrical therapy (e.g., high-voltage nanosecond pulseelectrical therapy). The treatment tips described herein may also bereferred to as applicators, applicator tips, retractable tips, or thelike.

Any of these apparatuses may include, for example: a treatment tiphousing; an electrode partition extending from a distal end of thetreatment tip housing, wherein the electrode partition is configured toretract proximally into the treatment tip housing; a bias holding or insome variations driving the electrode partition distally until anapplied force exceed a threshold; a plurality of treatment needleelectrodes within the electrode partition; the disal end of theelectrode partition may be electrically insulating, wherein theplurality of treatment needle electrodes is exposed through the distalelectrically insulating end when the electrode partition is drivenagainst a subject's tissue with a force exceeding the threshold force.As mentioned, this distal electrically insulating region may be aninsulating cover or sleeve.

As mentioned, the treatment tip housing may be formed of a rigid,polymeric or other material and may be configured as a unitary (e.g.,single piece) body, or it may be formed of multiple parts, e.g.,segments, etc.) coupled together. The treatment tip housing may extendproximally, and may include a proximal connection region for connecting(and particularly, releasably connecting) to a reusable applicatorhandle (“reusable handle”). The connection may be a mechanicalconnection for coupling the treatment tip (which may be single-use orlimited-use, e.g., disposable), such as a latch, snap, or the like. Thetreatment tip may be hollow.

The retractable treatment tip may include a retractable electrodepartition that extends from within a distal end of the treatment tiphousing. The retractable electrode partition may be configured to slideat least partially (or completely) into the treatment tip housing, andmay extend partially out of the apparatus. In general, the retractableelectrode partition may move relative to the other portions of thetreatment tip, and in particular, the retractable electrode partitionmay move relative to the treatment tip housing and treatment electrodes(e.g., treatment needle electrodes). The treatment electrodes may befixed relative to the treatment tip housing, or may be configured to belocked or fixed relative to the treatment tip housing in variations inwhich the treatment electrodes' penetration depth is fixed oradjustable, as will be described in greater detail herein. Theretractable treatment tip may partially or completely enclose thetreatment electrodes when the apparatus in not deployed. A distalelectrically insulating cover may be present on the distal end of theretractable electrode partition. The retractable electrode partition maybe configured to enclose and insulate the treatment electrodes.

All or some, e.g., the distal (e.g., subject-facing) end of theretractable electrode partition, may be electrically insulating, asmentioned. This electrically insulating distal end may be configured tobe soft, and in some cases may be deformable. For example, theelectrically insulating end may be a material having a durometer of 60or less on the Shore A hardness scale (e.g., a durometer of 55 or less,a durometer of 50 or less, a durometer of 45 or less, a durometer of 40or less, a durometer of 35 or less, or in some variations a durometer ofat least or greater than about 5, 10, 15, 20, 25, 30, 35 and less thanabout 40, 45, 50, 55, 60, etc.). The distal electrically insulating endmay also be referred to and may function as a distal contact pad formaking contact between the end of the distal electrically insulatingcover and the subject's tissue. As mentioned, the distal electricallyinsulating end is typically insulated, and may include or be entirelymade of an electrically insulating material having the desired hardness,such as one or more of: silicone, santoprene, or other TPE(Thermoplastic Elastomer) materials. In some variations the distal endof the electrode partition includes an electrically insulating cover.The cover may have the softness (e.g., durometer) within the rangesdescribed above.

The distal electrically insulating end may be connected to thedistal-facing (e.g., subject tissue-facing) end of the retractableelectrode partition and may therefore extend or retract with theretractable electrode partition.

The distal electrically insulating end may be of any thickness. Forexample, the distal electrically insulating end may be between about0.25 mm and 5 mm, (e.g., between about 0.25 mm and 3 cm, between about0.025 mm and 25 mm, between about 0.25 mm and 2 cm, between about 0.025mm and 15 mm, between about 0.25 mm and 10 mm, between about 0.25 mm and5 mm, etc.). The thickness may be uniform or non-uniform. The distal endface of the distal electrically insulating end may be flat orsubstantially flat. For example, the distal electrically insulating endmay be shaped to include one or more protrusions (rings, orgasket-regions) around any openings for the treatment electrodes throughthe distal electrically insulating cover. The distal electricallyinsulating end may form an electrical seal against the tissue toinsulate between the treatment electrodes between which energy is to beapplied (e.g., a first one or more electrodes and a second one or moreelectrodes), and in particular between treatment electrodes of differentelectrical polarities. For example, in some variations treatmentelectrodes of different electrical polarity pass through differentopenings in the distal electrically insulating end (and treatmentelectrodes of the same electrical polarity may pass through the sameopenings through the distal electrically insulating end). For example,ground treatment electrodes may pass through different openings in thedistal electrically insulating end than non-ground (e.g., “hot” orhigh/low) electrodes.

As mentioned, the treatment tip housing may include a proximal couplingregion configured to couple to an applicator. The proximal couplingregion of the treatment tip housing may couple the treatment tip to ahand-held applicator (a reusable treatment applicator), as mentioned. Inaddition, the proximal coupling region may make an electrical connectionbetween the high-voltage, high-pulse rate generator and the electrodesin the applicator tip (e.g., the plurality of treatment needleelectrodes). For example, the proximal coupling region may include aplurality of electrical connectors that are in electrical communicationwith the plurality of treatment electrodes.

The treatment electrodes may extend proud of the treatment tip housing(and/or proud of the electrode partition or electrode housing), in thedistal direction. In some variations the treatment electrodes may extendperpendicular of the electrode partition and/or the distal electricallyinsulating end of the electrode partition in the deployed configuration.In some variations the treatment electrodes may extend through thedistal electrically insulating end of the electrode partition. Forexample, the plurality of treatment electrodes may be configured toextend through an opening (or multiple openings) in the distalelectrically insulating end of the electrode partition when theelectrode partition is retracted. Alternatively, all or some of thetreatment electrodes may be extended through the distal electricallyinsulating end by penetrating (e.g., making a hole, puncture, slit, etc.in) the distal electrically insulating end; these punctures, slits, orholes may reseal when the retractable electrode partition is retracted.In general, the plurality of treatment electrodes may be held within thetreatment tip housing in an un-deployed state when the bias holds theelectrode partition distally extended from the treatment tip. Thus, thedistal tips (which may be sharp, e.g., tissue-penetrating, beveled, orrounded) of the treatment electrodes may be housed entirely within thetreatment tip housing and/or the electrode partition when the apparatusis not deployed, and force is not being applied to drive the retractableelectrode partition proximally or at least insufficient force toovercome the threshold force for deploying).

As mentioned, in any of the apparatuses described herein, the treatmentelectrodes may be adjustable. For example, the distal-to-proximal lengthof the plurality of treatment electrodes may be adjustable. Thetreatment tip and/or handle to which it connects may include a control(lever, dial, button, etc.) that advances or retracts the treatmentelectrodes so that they may extend more or less from the retractableelectrode housing or partition and/or distal electrically insulating endwhen the retractable electrode housing (or partition) is fully deployed.For example, the apparatus may include a screw mechanism to advance orwithdraw the treatment electrodes within the tip housing and/orelectrode partition.

In general, any number of treatment electrodes may be used (e.g.,typically 2 or more, 3 or more electrodes, 4 or more electrodes, 5 ormore electrodes, 6 or more electrodes, 7 or more electrodes, etc.). Thetreatment electrodes may be arranged in any configuration, including ina ring, row or two or more rows (parallel rows, crossing rows, etc.).The treatment electrodes may be any length (typically length refers tothe proximal-to-distal direction), including adjustable lengths, asdescribed above. For example, the treatment electrodes may be betweenabout 2 mm and 10 cm long (e.g., between about 2 mm and 9 cm, betweenabout 2 mm and 8 cm, between about 2 mm and 7 cm, between about 2 mm and6 cm, between about 2 mm and 5 cm, between about 2 mm and 4 cm, betweenabout 1 cm and 10 cm, between 1 cm and about 9 cm, between about 1 cmand 8 cm, between about 1 cm and 7 cm, between about 1 cm and 6 cm,etc.).

A treatment tip device for delivery of electrical therapy may include: atreatment tip housing having a proximal coupling region comprising aplurality of electrical connectors; an electrode partition extendingfrom a distal end of the treatment tip housing, wherein the electrodepartition is configured to retract proximally into the treatment tiphousing; a plurality of treatment needle electrodes within the electrodepartition in electrical communication with the plurality of electricalconnectors; and a bias within the treatment tip housing holding and insome variations driving the electrode partition distally with a biasreturn force so that the plurality of treatment needs are fully enclosedwithin the electrode partition; a distal electrically insulating end onthe distal end of the electrode partition, wherein the distalelectrically insulating end comprises a soft material, further whereinthe plurality of treatment needle electrodes are exposed through thedistal electrically insulating end when the electrode partition isdriven against a subject's tissue with a force exceeding the thresholdforce so that the electrode partition is driven proximally relative tothe plurality of treatment needle electrodes.

Also described herein are methods of treating a subject by applyingelectrical energy. These methods may include using any of the devicesdescribed herein. For example, a method of applying electrical therapyto a subject may include: positioning a treatment tip against thesubject's tissue so that a distal end face of an electrode partition(e.g., electrode housing) contacts the subject's tissue; driving thetreatment tip distally against the subject's tissue so that an electrodepartition (e.g., housing) retracts into a treatment tip housing while aplurality of treatment electrodes penetrates into the tissue distallypast the distal end face of the electrode partition (e.g., housing),wherein the distal end face of the electrode partition (e.g., housing)remains against the subject's patient to prevent arcing between theplurality of treatment electrodes by electrically isolating theplurality of treatment electrodes from each other. The method mayfurther comprise applying energy to the tissue from the plurality oftreatment electrodes.

As described above, the electrode partition may be an electrode housing.In any of these methods, the distal end face of the electrode partitionmay comprise a soft material, e.g., a material having a durometer of 60or less (e.g., 50 or less, 45 or less, 40 or less, etc.) on the Shore Ahardness scale. The distal end face of the electrode may comprise one ormore of: silicon, santoprene, or other TPE (Thermoplastic Elastomer)materials, or any other material providing a high resistance.

In any of these methods, driving the treatment tip distally may comprisedriving the treatment tip with a force that is greater than a thresholdforce necessary to overcome a bias holding the electrodehousing/partition extended from the treatment tip housing, in order todrive the electrode partition proximally relative to the plurality oftreatment electrodes. In variations in which the bias provides a returnforce (e.g., spring), the threshold force may be referred to as a biasreturn force; the threshold force may be between 0.01 pounds of forceand 10 pounds of force, as mentioned above.

Any of these methods may also include releasing a release lock to allowthe housing/partition to be retracted proximally into the treatment tiphousing.

In general, applying energy may comprise applying sub-microsecondelectrical pulses. For example, applying sub-microsecond electricalpulses may comprise applying a train of electrical pulses having a pulsewidth of between 0.1 nanoseconds (ns) and 1000 nanoseconds (ns). In somevariations, applying sub-microsecond electrical pulses comprisesapplying a train of nanosecond electrical pulses having peak voltages ofbetween 10 kilovolts per centimeter (kV/cm) and 500 kV/cm. For example,applying sub-microsecond electrical pulses may comprise applying a trainof sub-microsecond electrical pulses at a frequency of between 0.1 (Hz)to 10,000 Hz.

Any of the methods described herein may include coupling the treatmenttip to a reusable handle by connecting at least two electricalconnectors on a proximal end of the retractable treatment tip toelectrical contacts on the reusable handle.

Positioning the treatment tip against the subject's tissue may comprisepositioning the retractable treatment tip against the subject's skin.

The methods described herein include applying energy to treat one ormore indications. Any of the methods described herein may be methods fortreating (and may include one or more treatment steps for treating) oneor more of: any type of cancer, whether characterized as malignant,benign, soft tissue, or solid, and cancers of all stages and gradesincluding pre- and post-metastatic cancers (examples include, but arenot limited to, digestive and gastrointestinal cancers such as gastriccancer (e.g., stomach cancer), colorectal cancer, gastrointestinalstromal tumors, gastrointestinal carcinoid tumors, colon cancer, rectalcancer, anal cancer, bile duct cancer, small intestine cancer, andesophageal cancer; breast cancer; lung cancer; gallbladder cancer; livercancer; pancreatic cancer; appendix cancer; prostate cancer, ovariancancer; renal cancer (e.g., renal cell carcinoma); cancer of the centralnervous system; skin cancer, e.g., melanoma; lymphomas; gliomas;choriocarcinomas; head and neck cancers; osteogenic sarcomas; and bloodcancer; and/or Kaposi's sarcoma); dermatological procedures (e.g.,treating various dermatological conditions), such as skin cancers, agingskin, skin tumors, acne, seborrheic keratosis, keloids, molluscumcontagiosum, acrocordon, psoriasis, papilloma, human papilloma virus(HPV), melanoma, melasma, sebaceous hyperplasia (SH), syringoma,congenital capillary malformation (port-wine stains), congenital nevi,melasma, actinic keratosis, dermatosis papulosa nigra, angiofibroma,cherry angioma, warts, keloids/scars, aging skin, molluscum angioma,necrobiosis lipoidica (NBL), melisma, lipoma epidermal/sebaceous cyst,basal cell carcinoma; cosmetic skin treatments, including tattooremoval, hair follicle destruction, scar/keloids reduction, fatreduction, and wrinkle reduction.

Any of the methods described herein may also or alternatively includesetting a length of the plurality of treatment electrodes prior todriving the treatment tip distally against the subject's tissue.

In general, driving the treatment tip distally against the subject'stissue may include penetrating the electrically insulating cover by theplurality of treatment electrodes. Applying energy may comprise applyingelectrical energy without any insulating gel between the tissue and thetreatment tip.

In some variations, a method of applying electrical therapy to a subjectmay include: positioning a retractable treatment tip against thesubject's tissue, wherein the retractable treatment tip comprises anelectrode partition (e.g., an electrode housing) extending from a distalend of a treatment tip housing, the electrode partition having anelectrically insulting distal end, a plurality of treatment needleelectrodes having distal tips that are separated by the electrodepartition, further wherein the retractable treatment tip is in anun-deployed configuration in which a distal end of each of the treatmentneedle electrodes of the plurlaity of treatment needle electrodes areproximal to a distal end of the electrode partition; deploying theretractable treatment tip by moving the plurality of treatment tipelectrodes and the electrode partition relative to each other so thatthe distal end of each of the needle electrodes of the plurality oftreatment tip electrodes extend distally from the electrode partitionand into the subject's tissue wherein the electrically insulating distalend is applied against the tissue to electrically isolate the pluralityof treatment needle electrodes from each other; and applying energy tothe tissue from the plurality of treatment needle electrodes. Asmentioned above, the treatment tip apparatus may include a bias.

For example, a method of applying high-voltage nanosecond pulseelectrical therapy may include: positioning a retractable treatment tipagainst a subject's tissue, wherein the retractable treatment tipcomprises an electrode partition extending from a distal end of atreatment tip housing, the electrode partition having an electricallyinsulating distal end, a bias holding and in some variations driving theelectrode partition distally, a plurality of treatment electrodes (e.g.,treatment needle electrodes) separated by the electrode partition;pushing the retractable treatment tip against the subject's tissue witha force that is greater than the threshold force to drive the electrodepartition proximally relative to the plurality of treatment electrodeswhile penetrating the tissue with the plurality of treatment electrodesand driving the electrically insulating distal end against the tissue toelectrically isolate the plurality of treatment electrodes from eachother; and applying high-voltage nanosecond electrical pulses to thetissue from the plurality of treatment electrodes.

For example, a method of applying electrical therapy to a subject maycomprise: positioning a retractable treatment tip against a subject'stissue, wherein the retractable treatment tip comprises an electrodepartition extending from a distal end of a treatment tip housing, theelectrode partition having an electrically insulting distal end, aplurality of treatment electrodes (e.g., needle electrodes) within theelectrode partition, and a bias, further wherein the retractabletreatment tip is in an un-deployed configuration in which a distal tipof each of the plurlaity of treatment electrodes is within the electrodepartition; deploying the retractable treatment tip by moving theplurality of treatment tip electrodes and electrode partition relativeto each other so that the plurality of treatment tip electrodes extenddistally from the electrode partition and into the subject's tissue suchthat the electrically insulating distal end is applied against thetissue to electrically isolate the plurality of treatment electrodesfrom each other; and applying energy to the tissue from the plurality oftreatment electrodes.

Deploying may comprise releasing a release lock to allow the bias todrive the plurality of treatment needle electrodes distally.Alternatively or additionally, in some variations, deploying maycomprise pushing the retractable treatment tip against the subject'stissue with a force that is greater than a threshold force for the biasto holding the electrode partition (e.g., electrode housing) proximallyrelative to the plurality of treatment electrodes.

Any of the apparatuses described herein may be used without the need foran additional insulating gel (e.g., non-conductive gel) between thesubject's tissue and the apparatus, including the retractable treatmenttip. For example, any of these methods may include applying energy(e.g., high-voltage nanosecond electrical pulses) without any insulatinggel between the skin and the retractable treatment tip.

Any of these methods may include coupling the treatment tip (referred toherein as a “retractable treatment tip” as the electrode partition(e.g., electrode housing) region may retract away from the treatmentelectrodes) to a reusable handle by connecting at least two electricalconnectors on a proximal end of the retractable treatment tip toelectrical contacts on the reusable handle. The treatment tips describedherein may be configured so that the electrical connections connect asthe mechanical connection(s) are engaged. A lock or fastener may beincluded on either or both the treatment tip and/or reusable handle tohold the treatment tip engaged with the reusable handle. Any of thesemethods may include locking or removably securing the treatment tip tothe handle.

As mentioned, any of the methods described herein may be methods oftreating skin. For example, positioning the retractable treatment tipagainst the subject's tissue may include positioning the retractabletreatment tip against the subject's skin. Any of these methods maycomprise applying high-voltage nanosecond electrical pulses to thesubject's tissue to treat one or more of: organ tissue cancer, skincancer, cherry angioma, warts, keloids/scars, molluscum angioma,necrobiosis lipoidica (NBL), melisma, lipoma epidermal/sebaceous cyst,basal cell carcinoma, aging skin, benign tumors, and precanceroustumors. Alternatively, or additionally, these methods may be methods ofany other body tissue, including non-skin tissue (respiratory tissue,lung tissue, breast tissue, liver tissue, etc.).

The length of the electrodes may be selectable. Thus, any of thesemethods may include selecting the length of the plurality of treatmentelectrodes prior to pushing the retractable tip against the subject'stissue. In some variations the length of the insulation on theelectrodes may also be selectable/adjustable.

In some variations, the applicator may be pushed against the tissue withsufficient force to retract the electrode partition (e.g., electrodehousing) and to drive the electrodes into the tissue. The electrodes maybe driven into the tissue to a predetermined depth, which may be set bythe stop (e.g., preventing the electrode partition from retracting anyfurther, and therefore stopping the electrodes from pushing into thetissue any further. For example, pushing the retractable treatment tipagainst the subject's tissue with the force that is greater than thethreshold force to drive the electrode partition proximally relative tothe plurality of electrodes may comprise compressing a spring biaswithin the treatment tip housing to retract the electrode partitionproximally into the treatment tip housing so that the plurality oftreatment electrodes extend distally from the electrode partition. Thus,pushing the retractable treatment tip against the subject's tissue maycomprise penetrating the electrically insulating end by the plurality oftreatment electrodes.

The retractable treatment tip devices, particularly those having aretractable electrode partition as described herein, may reduce oreliminate arcing between the electrodes even when these electrodes arenot adequately coated with a non-conductive (e.g., insulating) material,such as a non-conductive gel. Allowing the electrodes to remainretracted into the treatment tip housing (and the retractable electrodepartition) when not in use or inserted into tissue may prevent arcingbetween the electrodes.

The apparatuses described herein may also include a soft rubber orsilicone tip (e.g., an insulating cover), as described above. Thisinsulating end may reduce arcing. For example, a soft rubber or siliconeat the tip may function like a Vaseline or other non-conductive gel toreduce arcing, thereby, improving the ease of use.

Thus, also described herein are insulating covers for a electrodes(e.g., needle electrodes), the insulating cover comprising: a soft bodyconfigured to fit over the distal end of a housing for an electrode,wherein the soft body comprises an electrically insulating materialhaving a durometer of 60 or less on the Shore A hardness scale; and achannel through the soft body configured to pass the electrode. The softbody may comprise a raised ring around the channel. The raised ring mayform a gasket. The soft body may have a durometer of 45 or less. In somevariations, the soft boy comprises a plurality of channels through thesoft body (e.g., configured to allow passage of each of the electrodes,e.g., in the distal-to-proximal direction).

The retractable treatment tip devices may also improve the safety forthe user during use or handling. With the electrodes housed within theelectrode partition when not in use, accidental scratching or puncturesmay be avoided. The retractable treatment tip devices may also reducethe likelihood of the treatment tip getting damaged during shipping orhandling.

The retractable treatment tip devices may include an adjustableelectrode length, as discussed above, which may allow users to customizethe depth of electrode penetration thereby customizing the depth of thelesion being treated. Alternatively or additionally, the insulationlength may be adjustable by the user. Adjusting the insulation length onthe electrodes may allow the user to adjust the active length, therebycustomizing the depth and size of the actual treatment.

Any of the retractable treatment tip devices may also include anextrusion in the tip that helps guide the electrode straight wheninserting into tissue. Longer electrode, and particularly needleelectrodes, may tend to veer off course when inserting them into tissue,however, having the electrode (e.g., needle) guides may hold theelectrode straighter during insertion making the treatment moreconsistent.

The applicator devices described herein may be used with one or more ofthe apparatuses (e.g., pulse generators) disclosed in any of theco-owned U.S. patent publication numbers: US 2017/0245928, US2017/0246455, and U.S. patent application Ser. Nos. 15/444,738 and15/347,728, all incorporated by reference herein in their entirety.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the disclosure are set forth with particularity inthe claims that follow. A better understanding of the features andadvantages of the present disclosure will be obtained by reference tothe following detailed description that sets forth illustrativeembodiments, in which the principles of the disclosure are utilized, andthe accompanying drawings of which:

FIGS. 1A-1E illustrate a first example of a retractable treatment tipdevice. FIG. 1A shows a side view. FIG. 1B is a perspective view of thedistal end face, showing the electrodes exposed. FIG. 1C is a proximalend view of the apparatus of FIG. 1A. FIG. 1D shows a partially explodedview of the apparatus of FIG. 1A. FIG. 1E is an exploded view of theapparatus of FIG. 1A.

FIG. 2A is a view of the retractable treatment tip device (similar tothe one shown in FIG. 1A) before coupling with a portion of a handleincluding a mechanical and/or electrical connection. FIG. 2B shows theretractable treatment tip device engaged with the portion of the handle.

FIG. 3A is an enlarged perspective view of an example of a distal end ofa retractable treatment tip device, showing the plurality of exposedneedle electrodes.

FIG. 3B shows an example of a side view of a retractable treatment tipdevice applied to tissue with a force against the tissue sufficient tocause the electrode housing (or electrode partition) to retract as thetreatment needle electrodes are driven into the tissue.

FIG. 4A shows an example of an enlarged perspective view of a distal endface of a retractable treatment tip device in which the treatment needleelectrodes are fully enclosed in the electrode housing.

FIG. 4B shows the retractable treatment tip device of FIG. 4A with aforce sufficient to overcome the bias holding the electrode housingportion of the retractable treatment tip device distally, exposing thetreatment needle electrodes.

FIG. 5A shows a side view of an example of a retractable treatment tipdevice driven against the tissue so that the sharp treatment needleelectrodes are inserted into the tissue while the electrode housing isbiased against the tissue (e.g., skin).

FIG. 5B is a side view of an example of a retractable treatment tipdevice in an un-deployed configuration.

FIG. 6A illustrates an example of a distal end of a retractabletreatment tip device including an insulating cover through whichelectrodes (e.g., needle electrodes) may be driven, as shown in FIG. 6B.

FIG. 7A is an example of a distal end of a retractable treatment tipdevice in an un-deployed configuration. FIG. 7B shows the distal end ofthe device in a deployed configuration, in which the electrodehousing/partition and insulating cover are retracted to expose theneedle electrodes.

FIGS. 8A and 8B illustrate examples of retractable treatment tipdevices, configured as disposable tips, coupled to a reusable handleapplicator portion configured as a gun.

FIG. 9 is another example of a retractable treatment tip device coupledto a reusable handle applicator configured as a pen.

FIGS. 10 and 11 show sectional views through one example of aretractable treatment tip device in an un-deployed (FIG. 10) and adeployed (FIG. 11) configuration.

FIG. 12A is a schematic example of a retractable treatment tip devicehaving an adjustable needle length.

FIG. 12B is a sectional view through a retractable treatment tip devicesimilar to that shown in FIG. 12A, having an adjustable needle length.

FIGS. 12C-12G illustrate an example of an expandable cam portion of aretractable treatment tip. FIG. 12C is an exploded view of theextendable cam portion of a retractable treatment tip. FIG. 12D is anassembled view of the extendable cam of FIG. 12C in a collapsed(non-expanded) configuration. FIG. 12E is an assembled view of theextendable cam of FIG. 12C in an expanded configuration. FIG. 12F showsthe extendable cam in a cam housing including a sliding control forextending a retracting the cam (and therefore any electrodes coupled tothe extendable cam). FIG. 12G shows the extendable cam of FIG. 12F inthe cam housing in an extended configuration.

FIGS. 13A-13B schematically illustrate variations of the distal ends ofretractable treatment tip devices including different insulating coverregions.

FIGS. 14A-14B schematically illustrate further examples of variations ofthe distal ends of retractable treatment tip devices including differentinsulating cover regions.

FIGS. 15A-15C schematically illustrate variations of the distal ends ofretractable treatment tip devices including different thicknesses ofsoft insulating cover regions. FIG. 15C also includes a guide channelregion for guiding the treatment needle electrodes into the tissue.

FIGS. 16A-16F illustrate an example of a method of using a retractabletreatment tip device to treat tissue (e.g., skin tissue).

FIGS. 16G-16L show another example of a method of using a retractabletreatment tip device to treat tissue (e.g., skin tissue) in which thedistal end of the retractable tip device is less soft than in FIGS.16A-16F.

FIGS. 17A and 17B show a perspective view of one variation of a distalend face of a retractable treatment tip device. In FIG. 17A thetreatment electrodes are at least partially enclosed in the insulatingelectrode partition that extends between a left set of electrodes and aright set of electrodes; in FIG. 17B the electrode partition isretracted, exposing the treatment electrodes and in particular, exposingthe space between the left and right sets of electrodes.

FIGS. 17C and 17D show side views of a variation of the retractable tipapparatus of FIGS. 17A and 17B.

FIGS. 18A and 18B show examples of a front perspective view of anothervariation of a distal end face of a retractable treatment tip device. InFIG. 18A, an un-deployed configuration, the treatment electrodes areseparated by the insulating electrode partition that extends between aleft set of electrodes and a right set of electrodes; in FIG. 18B, adeployed configuration, the electrode partition is retracted, exposingthe treatment electrodes and in particular, exposing the space betweenthe left and right sets of electrodes.

FIG. 19 is a schematic diagram illustrating an example of a method ofapplying high-voltage nanosecond pulse electrical therapy as describedherein.

FIGS. 20A-20B illustrate an example of an applicator handle that isconfigured as a gun and is configured for easy storage on a rim of atray or other holder.

FIGS. 21A-21C illustrates an example of a holster accessory device foruse with some examples of an applicator apparatus such as shown in FIGS.20A-B.

DETAILED DESCRIPTION

The methods and apparatuses described herein generally relate toelectrical treatment applications, and particularly electrodeapplicators having a plurality of electrodes (e.g., therapeuticelectrodes, including but not limited to therapeutic needle electrodes),in which the electrodes may be electrically isolated and/or protected byan insulated electrode partition (which may be configured as a housingin some variations) in an un-deployed configuration, and may be extendedinto a tissue relative to the electrode partition (e.g., housing) in adeployed configuration. The electrode housing may separate and protectbut does not necessary need to physically enclose the plurality ofelectrodes; in some variations, when the partition is configured as ahousing, it may fully or partially enclose all or some of the pluralityof electrodes. It should be understood that various examples referringto electrode housing are also applicable to the electrode partition andvarious examples referring to electrode partition are also applicable tothe electrode housing, unless the context makes it clear otherwise. Aswill be described in greater detail, the electrode housing or electrodepartition may operate as an insulating member that prevents electricalarcing between the electrodes, even without the need for additionalinsulating materials, such as an insulating gel, that may otherwise berequired.

Some of the apparatuses as described herein include a plurality ofelectrodes that may be exposed by applying force to retract an electrodepartition (e.g., electrode housing) relative to the electrodes (e.g., bydriving the electrode housing or partition against the tissue to betreated). The electrodes may be fixed relative to a treatment tiphousing, so that driving the device against the tissue drives theelectrodes into the tissue and pushes the electrode housing or partitionback to expose the electrodes beyond the distal end of the electrodepartition (e.g., housing). Alternatively or additionally, it should beunderstood that the electrodes may be retractable and extendablerelative to the treatment tip housing. For example, the electrodes maybe coupled to a bias that can be actuated by a control on the apparatusto extend or retract the electrodes out of the treatment tip housingand/or to extend or retract the electrode housing (or partition) intothe treatment tip housing. In some variations the electrode housing orelectrode partition may be fixed relative to the treatment tip housing,and the electrodes may be movable. In some variations, the electrodesmay be configured as part of an auto-injecting assembly in which theelectrodes are biased (e.g., by a mechanical, electrical, pneumatic orother bias) against a release control (such as a button); when therelease control is pressed, the electrodes may be ejected into thetissue to be treated. The electrodes may be limited by a hard stop andremain within the housing of the disposable tip.

In many of the examples provided herein the apparatus may include a biasthat retains the electrode partition (e.g., electrode housing) in anun-deployed configuration with the distal face of the electrodepartition, which may be soft and/or electrically insulating, extendingdistally beyond the distal tips of the plurality of electrodes. The bias(which may also be referred to as a retaining bias) may be overcome byapplying a force greater than a threshold force. Once the applied force(e.g., by pressing the device against the tissue) is met or exceeded,the electrode partition (e.g., housing) may retract into the treatmenttip housing, allowing the electrodes to extend distally beyond thedistal face of the electrode partition and into the tissue. The distalface of the electrode partition (e.g., housing) may stay pressed againstthe tissue, helping electrically isolate the different electrodes (orsets of electrodes) in the plurality of electrodes.

In any of the apparatuses described herein, the distal-facing end of thetreatment tip may be electrically insulating. Specifically, the distal(tissue-contacting) face of the electrode partition (e.g., housing)includes an electrically insulating distal end region. Furthermore, therelative movement between the plurality of electrodes and the electrodehousing may allow the electrodes to be held in a protected configurationin which the distal ends of the electrodes are fully housed within theinsulating electrode housing; the apparatus may then controllablyconvert to a deployed configuration in which the electrodes are extendedout of the treatment tip housing and/or the electrode housing. In thedeployed configuration, the electrodes may be fully extended to a stopposition between the electrode housing and the electrodes; insulation onthe distal facing end of the electrode housing may surround theelectrodes, thus when pressing the apparatus into the tissue the distalfacing end of the electrode housing may be pushed against the tissuewhen the electrodes are fully engaged with the tissue, insulating themand preventing arcing. For example, described herein are retractabletreatment tip apparatuses (e.g., devices, systems, etc.) including one,or more, preferably a plurality, of electrodes that are protected by andmay be enclosed inside a housing until delivery of a therapeutictreatment. These apparatuses may include a plurality of treatment needleelectrodes (“needle electrodes”) and be configured for the delivery ofnanosecond pulsed electric fields (nsPEF, or sometimes referred to assub-microsecond pulsed electric fields), which may include an electricfield with a sub-microsecond pulse width of between 0.1 nanoseconds (ns)and 1000 nanoseconds, or shorter, for example, 1 picosecond. NsPEFsoften have high peak voltages, such as 10 kilovolts per centimeter(kV/cm), 20 kV/cm, to 500 kV/cm. Treatment of biological cells withnsPEF technology often uses a multitude of periodic pulses at afrequency ranging from 0.1 per second (Hz) to 10,000 Hz. However,although the apparatuses described herein are adapted for, andparticularly well suited for the delivery of therapeutic nsPEF, they mayalso be used as electrodes to deliver other therapeutic treatments,including treatments with continuous (non-pulsed) energy, and treatmentsusing slower than nanosecond pulses (e.g., microsecond, millisecond, orlonger duration pulses).

The apparatuses described herein may be used to deliver one or morensPEF treatments to treat various disorders and disease, including butnot limited to cancer. It has been shown that nsPEF may be used to treatcancerous tumor cells; selectively and specifically driving them toundergo apoptosis, a programmed cell death, causing tumors to shrink tononexistence after treatment. It has also been shown that the subject'simmune system may be stimulated to attack all similar tumor cells,including those of tumors that are not within the nsPEF-treated tumor.In general, a disease may include any abnormal condition in or on asubject that is associated with abnormal, uncontrolled growths oftissue, including those that are cancerous, precancerous, and benign, orother diseases as known in the art. Apoptosis of a tumor or cellincludes an orderly, programmed cell death, or as otherwise known in theart.

As used herein, a “tumor” includes any neoplasm or abnormal, unwantedgrowth of tissue on or within a subject, or as otherwise known in theart. A tumor can include a collection of one or more cells exhibitingabnormal growth. There are many types of tumors. A malignant tumor iscancerous, a pre-malignant tumor is precancerous, and a benign tumor isnoncancerous. Examples of tumors include a benign prostatic hyperplasia(BPH), uterine fibroid, pancreatic carcinoma, liver carcinoma, kidneycarcinoma, colon carcinoma, pre-basal cell carcinoma, and tissueassociated with Barrett's esophagus.

In general, any of the apparatuses described herein may be connected toand used with a pulse generator. The retractable treatment tipsdescribed herein may be disposable and may be configured for a single orlimited use (e.g., single use, single session use, etc.). Theretractable treatment tips may be configured to connect or couple(electrically and/or mechanically) to a reusable applicator device, suchas a handle connected to a control system including a pulse generator.The control system may control delivery of electrical pulses through theretractable treatment tip. These apparatuses may be particularly welladapted for delivery of high-energy (high voltage) pulse lengths, forexample, of between 10 and 900 nanoseconds, including pulse lengths ofbetween 50 and 300 nanoseconds, or about 100 nanoseconds.

For example, a nanosecond pulse generator system may include any of theretractable treatment tips described herein (“electrodes”), a usercontrol input (e.g., footswitch) and user interface (display, monitor,speaker, etc.). The user control input and interface may be connected tothe control circuitry within a housing that holds the electroniccomponents. The retractable treatment tips may be connected to thecontroller and the electronic components therein through a high voltageconnector. Examples of such high voltage connectors are described in theco-pending and co-owned International patent applicationPCT/US2017/052340, which is herein incorporated by reference in itsentirety. The user may input or select treatment parameters, such as anumber of pulses, amplitude, pulse duration, and frequency information,via one or more input devices, such as a numeric keypad, touch screen,mice, track pad, stylus, pen, speaker, etc.

A retractable treatment tip for high-voltage electric therapy, such asnanosecond pulse electrical therapy may include a treatment tip housing,an electrode partition, and a plurality of treatment electrodes withinthe electrode partition. The retractable distal tip may also comprise adistal electrically insulating cover on the distal end of the electrodepartition, wherein the plurality of treatment electrodes may be exposedthrough the distal electrically insulating cover. In some embodiments,when the electrode partition (e.g., housing) is driven against asubject's tissue with a force exceeding a threshold force, the electrodepartition may retract and the plurlaity of electrodes may be drivendistally relative to the distal end face of the electrode partition andinto the tissue. Alternatively or additionally, the electrodes may becoupled to a constrained electrode bias (e.g., needle bias) that maydrive the electrodes from out of the distal end of the treatment tiphousing and/or electrode partition when released from the constrainedconfiguration. The bias constraint may be released by a button or othercontrol (e.g., on the apparatus) activated by the user, and may drivethe electrodes distally with the electrode bias force, which maypenetrate the tissue if the electrode partition is pressed against thetissue.

FIGS. 1A-1E illustrate one example of a retractable treatment tip. InFIG. 1A, the treatment tip is generally elongate (extending proximallyto distally) and includes a treatment tip housing 101, having a slightlyelongated, tapered shape. An electrode partition (configured in thisexample as a housing) 103 extends from the distal end of the treatmenttip housing. A mechanical connector on the proximal end 110 may couplewith a handle, as will be described in detail below, and may alsoinclude one or more electrical connectors for coupling with theelectrodes housed within the treatment tip housing and/or electrodehousing, which may extend from the treatment tip housing and/orelectrode housing as shown in FIG. 1B. FIG. 1B shows a close-up of theelectrode housing 103, which is shown having a rectangular cross-section(any shape cross-section may be used). The distal-facing (e.g., tissuefacing) end of the electrode housing may be covered by an insulatingcover 107. A plurality of treatment needle electrodes 105 are shownprojecting from the at least partially retracted electrode housing. InFIG. 1B, the electrodes are needle electrodes that may have a sharp andbeveled distal end but are cylindrical needles. However, the needleelectrodes are shown by example only and any type and shape of electrodemay be used. The electrodes may be insulated or un-insulated; in somevariations the treatment electrodes are insulated along a portion oftheir length, but the distal end (e.g., the distal 0.5 mm, 1 mm, 1.2 mm,1.5 mm, 1.7 mm, 2 mm, etc.) are un-insulated. FIG. 1C shows the proximalend 110 of the retractable treatment tip. In this example, theretractable treatment tip includes a mechanical connector 111 (shown byexample as a snap or latch) that couples the retractable treatment tipto a handle. The retractable treatment tip also includes two electricalconnectors 113, 113′. This proximal end of the retractable treatment tipmay couple with the handle to make both mechanical and electricalconnection.

Within the retractable treatment tip housing 101, in some embodimentsthe plurality of electrodes may form part of an electrode assembly thatis coupled to the treatment tip housing so that the electrodes arelocked in position relative to the treatment tip housing, but not theelectrode housing 103. In this example, a bias 117 (shown in thepartially exploded view of FIG. 1D by example as a spring) may be usedto apply a bias return force against the electrode housing, to push theelectrode housing distally. The electrode housing 103 may engage withthe treatment tip housing 101 so that it can otherwise slide proximallyand distally. For example, the electrode housing and treatment tiphousing may slide relative to each other via a channel formed in thetreatment tip housing in which a projecting region in the electrodehousing slides. Alternatively or additionally, the channel may be in theelectrode housing and the projection may extend from the treatment tiphousing. In general, the bias may hold the electrode housing distallyextended until it reaches a stop position; in some variations amechanical stop may be included to prevent further distal advancement.The electrode housing may be driven proximally by applying force(typically normal to the distal-facing end of the electrode housing) tothe electrode housing. For example, by pushing the distal facing end ofthe electrode housing against the tissue when holding the treatment tiphousing (e.g., coupled to a handle).

FIG. 1E is an exploded view of the retractable treatment tip exampleshown in FIGS. 1A-1D. The distal portion of the treatment tip housing101 connects with a proximal portion 114 of the treatment tip housing toenclose the bias 117 and at least a portion of the electrode housing, aswell as the plurality of electrodes (e.g., a first set of one or moreelectrically connected needle electrodes 119, and a second set of one ormore electrically connected needle electrodes 119′) and electricalconnectors (not shown). In this example, the mechanical connector 111may be used to couple the retractable treatment tip to a handle (e.g., areusable handle). In the example of FIG. 1E, the electrode housingincludes projections 116 that slide within the outer treatment tiphousing 101, e.g., in channels within the treatment tip housing. Aspacer 118 may be used to limit the relative movement between thetreatment tip housing and the electrode housing. The two halves of theouter treatment tip housing may be connected permanently or removably.

The retractable treatment tips described herein may come in a variety ofdifferent sizes and configurations that may be used in multipleindications. For example, the size (e.g., diameter) of the treatmentarea on the distal face of the apparatus may be varied (e.g., betweenabout 1 mm to 20 mm), and may be any appropriate shape (e.g.,rectangular, rounded, triangular, oval, etc.). The treatment electrodes(e.g., needle electrodes) may be any appropriate length, and may be afixed length or the length may be adjustable. For example, the lengthmay be between about 0.2 mm and 60 mm. The diameter of the electrodesmay be any appropriate diameter, e.g., a maximum cross-sectionaldiameter of between about 0.02 and 1 mm. The treatment electrodes may beinsulated. The distal-facing (e.g., flat or beveled) face is typicallynot insulated, but in some variations a distal-facing length of thetreatment needle electrodes extending from the distal end of thetreatment needle proximally may be uninsulated as well. For example, thedistal end of the electrode may be uninsulated to leave an exposedlength of between about 0 mm and 20 mm. The length of the insulation maybe variable and/or adjustable. For example, the length of the insulationof the electrodes may be controllably adjusted to between about 0 mm andabout 20 mm.

As mentioned, the retractable treatment tip (e.g., a disposabletreatment tip) is generally configured to couple with a reusable handle.FIGS. 2A-2B illustrate mechanical and electrical coupling between aretractable treatment tip 200 and a portion of a reusable handle 205. Aconnector 211 (shown by example as a clip in FIGS. 2A-2B) maymechanically and releasably secure the retractable treatment tip and thehandle together.

The retractable treatment tips may be configured to attach to anyappropriate handle, as will be shown in greater detail in FIGS. 8A-8Band 9, below.

FIG. 3A shows another view of an example of the distal end of aretractable treatment tip, including an insulating cover 307 that coversthe distal-facing end of the electrode housing 303 with a layer of soft,insulating material. The electrode housing 303 may be held distally outof the treatment tip housing 301 by a bias (e.g., a spring in thisexample) that is capable of applying a biasing return force B (shown inFIG. 3A), but pushing against the biasing return force (e.g., by drivingthe retractable treatment tip against the tissue to be treated whileholding the handle to which the retractable treatment tip is coupled)may push the electrode housing proximally allowing the treatmentelectrodes to be driven distally into the tissue. In FIG. 3A, the needleelectrodes 305 are shown deployed out of the electrode housing,presumably because a force greater than the threshold force to overcomethe bias (e.g., “F” in FIG. 3A) is applied against the distal face ofthe electrode housing 307. In practice, this may be achieved by pushingagainst a tissue. This is illustrated in FIG. 3B. In this example, thethreshold force is equivalent to the biasing return force, B′. Theapparatus shown in FIGS. 3A-3B is held proximally by a handle or by thetreatment tip housing portion and force, F, is applied to drive theelectrode housing 303 against the tissue 350 by pushing the device intothe tissue. This allows the electrodes 305 to be driven into the tissue350 while pushing the soft insulating cover 307 portion of the apparatusagainst the tissue between the electrodes, insulating them relative toeach other. As the electrode housing is retracted into the treatment tiphousing 301, the electrodes extend into the tissue. The bias returnforce B′ (arrow in FIG. 3B) opposing the applied force F′, and sine theapplied force is greater than the threshold force (in this case B′), theelectrode housing is retracted while the needle electrodes are extendedinto the tissue. In this example, the electrode housing distal face isdriven against the skin with the bias return force B′.

FIGS. 4A and 4B illustrate another example of a retractable treatmenttip. In FIG. 4A the distal end of the apparatus is shown with theelectrode housing 403 fully extended distally. An internal spring (notshown) may bias the electrode housing distally, holding it in theun-deployed configuration and providing a bias return force to restorethe un-deployed configuration. The electrode housing may include adistal insulating cover 407 that, in this example, has a plurality ofopenings or holes 416 through which treatment electrodes 405 may extendwhen the housing is pushed (by a force greater than the threshold force,in this example equivalent to the biasing force) into the distal end ofthe treatment tip housing 401. In this example the side of the electrodehousing may include one or more fiducial markers 418 that mark therelative position of the electrode housing relative to the treatment tiphousing 401 and/or the relative position and orientation of thetreatment electrodes on the tip. For example, in FIGS. 4A and 4B, thetwo fiducial lines 418, 418′ on the tops of the electrode housing 403are aligned with the rows of needle electrodes once they exit theelectrode housing. In this way, the user may know where the rows ofneedle electrodes are. The fiducial line 418″ on the adjacent side is inthe middle of the two rows of needles. The top of these lines mayindicate the fully retracted position of the electrode housing and/orthe fully extended position of the needle electrodes when deployed. Someor all of these fiducial markers (e.g., lines) on the electrode housing,or other markers on the electrode housing, may show how far theelectrode housing is retracted, and/or how far the electrodes have beeninserted into the tissue. For example, lines transverse to the elongatelength (e.g., of fiducial lines 418, 418′, 418″) may include indicatorsfor the electrode depth. The fiducial markers described in reference toFIGS. 4A and 4B may be used in any of the examples, embodiments andimplementations described herein.

FIGS. 5A-5B illustrate another example in which the treatment tip ispushed against a tissue 550 with sufficient force to drive the treatmentelectrodes into the tissue as the electrode housing 503 is pushedproximally and the soft, insulating distal face of the electrode housingis driven against the face of the tissue being treated so that itretracts into the treatment tip housing 501, as shown. In FIG. 5B, theapparatus 500 is shown in the un-deployed configuration. Two electricalconnectors 536, 536′ are also shown on the proximal end of theapparatus, shown in this example as male connectors that connect to thetreatment electrodes.

In the example shown in FIGS. 4A and 4B, above, the distal end of theelectrode partition is covered by an insulating cover that includesholes or opening through which the electrodes may extend when theelectrode housing is pushed proximally. In some variations theinsulating cover does not include holes or openings and instead thetreatment electrodes penetrate into and through the soft insulatingcover itself. For example, the soft insulting cover may be silicone,santoprene, or other TPE (Thermoplastic Elastomer) materials. This isillustrated in FIGS. 6A-6B. In FIG. 6A the soft insulating cover 607 issmooth, and does not yet have any openings through it. Retracting theelectrode housing 603 by pushing against it with sufficient force toovercome any bias from, e.g., a spring within the housing, as well asthe force required to penetrate the thickness of the insulating coverallows the treatment electrodes 605 to extend out of the insulatingcover, as shown in FIG. 6B.

FIGS. 7A and 7B illustrate another example of a distal end of aretractable treatment tip device in which the apparatus includes aplurality of treatment needle electrodes 705 extending through athickness of soft insulting cover 707 forming the distal end of theelectrode housing 703 that extends distally from the distal end of thetreatment tip housing 701. In FIG. 7A, the border 729 of the insulatingcover 707 which may extend partially up the lateral side of one or moreof the sides of the electrode housing may be used to confirm deployment(e.g., retraction of the electrode housing and insertion of the needleelectrodes into the tissue). As shown in FIG. 7B, when applied againstthe tissue (not shown), the border 729 may align with the distal end ofthe treatment tip housing 701 when the needles 705 are fully deployed.Alternatively or additionally, when the two parts of insulating cover707 that wrap around the fiducial line 718 can be longer and when thosetwo wrap-around features are in-line with the treatment tip housing 701,the needles are fully deployed. Thus, in any of the variations describedherein, a fiducial marking (e.g., line) may indicate that the electrodesare fully deployed. This may be particularly beneficial, as theelectrodes may be fully deployed into the tissue and not visible to theuser. A visual indicator that the electrodes are fully deployed may beused to determine when treatment should be triggered.

FIGS. 8A-8B illustrate a first example of a reusable handle for an nsPEFapplicator system. In FIGS. 8A and 8B, the handle 808 is configured as agun-shaped body that couples to a treatment tip 800, as shown. Thetreatment tip includes an electrode partition 803 (including aninsulating, distal-facing portion 807 that may be soft and/orcompliant). The electrode partition includes openings 841 through whichthe treatment electrodes may extend. The reusable handle may include oneor more controls 848, 848′ that may be used to control the delivery ofelectrical energy through the electrodes. In some variations theapparatus may be configured to prevent or limit the application ofenergy through the treatment electrodes until and/or unless theelectrode partition is retracted (or retracted past a particular depth)or the electrodes are extended (or at least partially extended). Theapplicator handle shown in FIGS. 8A-8B may be connected (e.g., via acable or cables, not shown) to a pulse generator and/or controller.

FIG. 9 illustrates another embodiment of a reusable applicator handle908, for example, for an nsPEF that couples (mechanically and/orelectrically) to a treatment tip 901 having a retractable electrodepartition 903, which may be similar to any of those electrode housingsdiscussed above or similar to a partition 1803 shown in FIG. 18 below.In this example, the applicator handle may be a pen or a cylinder-shapedbody. One or more controls (not shown) for controlling the depth ofpenetration of the treatment electrodes, e.g., a dial, lever, slider,etc. that moves the stop for the treatment housing and/or the relativeposition of the electrodes within the treatment tip housing.

The treatment tip may include a plurality of electrical connectors thateach connect one or more treatment electrodes to the pulse generatorthrough the reusable handle. For example, FIGS. 10 and 11 illustratetreatment tips 1100, shown in cross-sectional views, that include a pairof electrical connectors 1171, 1171′ that are wired 1173 (e.g., viewire, post or other electrical connector) to connect to the treatmentelectrodes 1105, as shown in FIG. 11. In the sectional view shown, thebias 1117 is connected between the treatment tip housing 1102, 1101(formed from two connected portions) and the retractable electrodepartition 1103 (configured as a housing in this example). The bias inthis example is a spring. The treatment tip housing may include aninternal stop 1115 for limiting the proximal movement of the electrodepartition, as shown in FIG. 11B, in which the electrode housing is fullyretracted when a force that is greater than the threshold force drivingthe electrode partition distally is applied. The stop 115 engages a lip,rim or edge 1104 on the housing. The treatment needle electrodes(electrodes) may form an electrode assembly 1175, 1175′ that in someembodiments may be coupled 1108 to the treatment tip housing so that itdoes not move relative to the treatment tip housing as the treatment tipis driven distally with sufficient force to retract the electrodepartition. In the retracted state, the electrode array (e.g., needleelectrode array) sits at the distal end of the tip, recessed inside thesoft, elastomeric tip in some variations (e.g., the insulating distalend region). The proximal end of the needle array shown in FIGS. 10 and11 includes electrical connectors configured as male pin terminals thatmay connect to the handle. The apparatus may include a spacer (notshown) that may limit the fully extended position of the electrodepartition within the treatment tip housing in the un-deployedconfiguration.

As discussed above, in any of the treatment tips described herein, thepenetration depth of the treatment electrodes may be adjustable. Forexample, the length of the treatment tip electrodes that extends fromthe electrode partition when the retractable electrode partition isfully retracted may be adjustable. FIG. 12A illustrates one example of atreatment tip including an adjustable electrode length. In FIG. 12A, acontrol (dial 1205) on the treatment tip allows it to be adjusted byrotating a ramp or surface 1265 within the treatment tip. Either or boththe electrode assembly position may be adjusted, e.g., adjusting therelative positions of the treatment electrodes within the treatment tiphousing 1201, or the position of the stop for the proximal retraction ofthe electrode partition 1203 into the treatment tip housing 1201 may beadjusted. For example, by rotating a dial (such as dial 1205 in FIG.12A), the stop location may adjust proximally/distally and may changethe total electrode deployment length. In any of the variations shownherein, the length of the insulation on all or some of the treatmentelectrodes may be adjusted by a control (e.g., dial, slider, knob, etc.)on the treatment tip.

FIG. 12B shows a cross sectional view of another example of a treatmenttip 1200 having adjustable length electrodes, similar to that shown inFIG. 12A. In FIG. 12B the device includes many of the same elements asin FIG. 11 (e.g., electrodes 1105, electrode housing 1103, treatment tiphousing 1102′, 1101, electrode assembly 1175, 1175′, electricalconnectors 1173, and bias 1117). However, in FIG. 12B, the device mayalso include an expandable cam portion including a cylindrical camassembly 1263 with one or more ramps and a control tab lever 1258 shownin cross section. The cylindrical cam follower 1278 portion of thecylindrical cam assembly 1263 may be positioned between a modifiedproximal housing 1102′ and the electrode housing 1103, and may includeone or more controls (e.g., control tab/lever 1258) extending through aslot 1212 (see FIG. 12F-12G, not visible in FIG. 12B), in the distalhousing portion. FIGS. 12C-12G show an example of a cylindrical camassembly 1263 that may be used for extending or retracting theelectrodes. The cylindrical cam assembly 1263 may be similar to thatshown in FIG. 12B. An electrode assembly may include one or moreguide/stop tabs 1276, 1277 (seen in FIG. 12B) that when retracted mayride on top of (come in contact with) the surface of the cylindrical camfollower 1278, such that the retraction stop dimension may be set by theposition of the cylindrical cam rotational position as controlled bycontrol tab (lever) 1258.

For example, in FIG. 12C a schematic perspective view of one example ofa cylindrical cam assembly 1263 includes an outer cylindrical cam 1255having two ramps 1256, 1257 on its distal circumference. A control tab(lever) 1258 may be integral with the cylindrical portion of the of thecylindrical cam element. The electrodes (electrode assembly) may be incontact with either the top or bottom of the cylindrical cam assembly(e.g., the cam follower 1278 or the outer cylindrical cam 1255), whilethe other one of the top or bottom of the cylindrical cam assembly 1263may be connected to the tip housing or other reference surface. Forexample, the cylindrical cam follower 1278 portion of the cam assembly1263 may include two guide/stop tabs 1270, 1271 on opposing sides of theelectrode partition. The guide/stop tabs 1270, 1271, may move withinaxial guide slots (cam surfaces) in an inner wall of a distal housing(not shown in FIG. 12C-12D, but see FIG. 12F-12G), and may not rotate.The guide/stop tabs 1270, 1271 may ride on the top of the respectivecomplimentary cam ramps 1256, 1257 causing the electrode assembly and/orthe electrode housing to extend and retract or move in a distal or aproximal direction relative to the treatment tip housing as the control1258 is moved.

FIG. 12D is a schematic perspective view of the extendable cam assembly1263 shown in FIG. 12C. In FIG. 12D, the inner cam follower 1278 isengaged with the outer cylindrical cam 1255 having its control (e.g.,knob or lever) 1258 rotated to a position where the guide/stop tabs1270, 1271 ride on the top of the respective complimentary cam ramps1256, 1257 to their lowest (most proximal position). In FIG. 12E, whenthe control (e.g., lever) 1258 is rotated (as shown by the arrow fromright to left in FIG. 12G) to a most extended control position, theguide/stop tabs 1270, 1271 ride on the top of the respectivecomplimentary cam ramps 1256, 1257 to a highest (most distal) location,extending the extendable cam.

FIGS. 12F and 12G include an outer housing 1211 outside of the inner1278 and outer 1255 cylindrical cam elements. The outer housing may bepart of or connected to the treatment tip housing. In FIG. 12F, a slot1212 in the outer housing 1211 is visible, through which a control 1258can extend.

In use, the distal end of the soft distal end of the electrode partitionmay be configured as an insulator. This insulator maybe an insulatorcover, as described above, or it may be the material from which theentire electrode housing or electrode partition, or at least a distalend portion of the electrode housing or electrode partition, is formed.FIGS. 13A-13B and 14A-14B illustrate alternative variations of electrodeinsulators, including distal insulators and covers. In FIG. 13A thedistal end face of the electrode partition 1309 is an insulator 1407that is formed of a soft material that can be driven against the tissue.The insulator may include openings for one or more of the treatmentelectrodes 1405, shown connected to an electrode assembly 1475, 1475′.The soft insulator 1407 may be pushed against the tissue and may conformto the tissue surface, even if the tissue surface is slightly irregular.

In some variations the distal end face of the electrode partition mayinclude one or more vacuum ports through which suction may be drawn tohelp secure the electrode partition against the tissue to preventshorting (arcing) between the treatment electrodes. In FIG. 13B, theinsulator 1407′ includes passages forming the suction ports 1474, 14751476, 1477. The ports may extend via tubing (e.g., flexible tubing) upto a suction source in the handle or controller. In other embodiments,the suction ports that help to secure the electrode partition againstthe tissue to prevent arcing may be used on their own without theinsulator. In those embodiments, the suction ports may be formed throughthe electrode partition to the distal end of the electrode partition.

In FIG. 14A, the retractable electrode partition 1409 includes a soft,insulating distal face (shown as a cover 1407″) that includes a sealingregion 1487, 1487′ around the distal-facing treatment electrode openings1488, 1488′. In some variations these sealing regions are projectionsand may be ring-shaped or continuous around the openings to permit themto seal and electrically insulate the treatment electrodes.

As discussed above in reference to FIGS. 6A-6B, in some variations theinsulating cover may not include defined openings, but may be configuredto be penetrated by the treatment electrodes when the electrodehousing/partition is retracted or the electrodes are extended. Anotherexample of this configuration is shown in FIG. 14B, showing aninsulating cover 1407′″ that is solid, but may be formed of a materialthat can be penetrated by the treatment electrodes 1405.

In general, the insulator (e.g., insulating cover or insulating distalend) of the retractable electrode partition maybe any appropriatethickness. In some variations, particularly those in which theinsulating distal end/cover are relatively thin, a guide (e.g.,electrode guide, needle electrode guide, etc.) may be included to guidethe electrodes as they extend through and out of the treatment tiphousing and/or electrode partition, preventing bending. For example,FIGS. 15A-15C illustrate retractable electrode partitions 1509 havingsoft, insulating covers of varying thicknesses 1502, 1502′, 1502″. Thevariation of the insulating cover 1507 shown in FIG. 15A is similar tothat shown in FIG. 13A. For comparison, FIG. 15B shows an example of anapparatus having a slightly thinner 1502′ soft, insulating cover 1507′.Finally, in FIG. 15C, the soft insulating cover 1507″ is thinner 1502″than that shown in FIG. 15B. In FIG. 15C the electrode partition alsoincludes an electrode guide 1584 (or a plurality of electrode guides).The electrode guides may be proximal to the soft, insulating cover, andmay be made of a more rigid material. In variations in which a separateinsulating cover is used at the distal face of the electrode partition,the insulating cover may be any appropriate thickness. For example, theinsulating cover may have a thickness (in the distal-facing direction)of between about 0.25 mm and 5 mm.

In use, any of the apparatuses shown herein may be configured to applyenergy (e.g., nsPEF) to a tissue. For example, any of these apparatusesmay be used to treat a tissue such as skin, liver, lung, breast, etc.,or treat a disorder or disease such as cancer. For example, any of theseapparatuses may be configured to apply energy to treat a disease, forexample, a disease related to dermatology and/or oncology, such as skincancer, cherry angioma, warts, keloids/scars, aging skin, molluscumangioma, necrobiosis lipoidica (NBL), melisma, lipomaepidermal/sebaceous cyst, basal cell carcinoma.

The use of an applicator tip having a retractable electrode housing orelectrode partition as described herein may be particularly beneficial.For example, the apparatus may be configured to conform to anirregularly-shaped or textured surface while preventing arcing, whichmay otherwise be dangerous and painful to the subject. For example,FIGS. 16A-16F illustrate the use of a retractable (biased) electrodepartition extending from the distal end of the apparatus. In FIG. 16A,the distal end of the applicator tip 1603 is brought in proximity to thetissue 1691, in which a target region 1693 to be treated is present.Thus, the entire applicator tip may be driven with force 1655 againstthe tissue, as shown in FIGS. 16B-16C, first to contact the tissue, thento continue to apply force 1656, which may allow the soft (e.g.,semi-compliant) distal-facing insulator of the applicator tip 1603 toconform to the surface of the tissue 1691 to be treated.Distally-directed force 1656 may be applied, as shown in FIG. 16D, todrive the electrodes 1605 into the tissue while pushing and retractingthe electrode partition proximally, allowing the electrodes to penetratethe tissue and the insulator to insulate between them. Once theelectrodes have been positioned (in this example in FIG. 16E to amaximum depth allowed by the retracted electrode partition), power,including in particular nsPEF therapy, may be applied. Thereafter, theapplicator tip may be withdrawn, as shown in FIG. 16F by arrow 1657; anytherapeutic effect on the treatment site 1693 may result eitherimmediately or within a reasonably short time period.

In FIGS. 16A-16F, the distal-facing, soft insulating end (e.g., cover)on the electrode partition 1609 is sufficiently soft that it deforms tofit the tissue, as shown in FIGS. 16B-16C. For example, the durometer ofthe soft, insulating cover may be less than about of 60 or less on theShore A hardness scale (e.g., about 55 or less, about 50 or less, about45 or less, about 40 or less, etc.). Alternatively, in some variationsthe hardness of the insulating cover may be greater than the hardness ofthe tissue, so that the tissue may deform (or both the tissue and thesoft insulating cover may deform). FIGS. 16G-16L illustrate an examplein which the tissue and the soft insulating cover both deform. In FIG.16G, the distal end of the applicator tip 1603′ is brought in proximityto the tissue 1691′, in which a target region 1693 to be treated ispresent. Thus, the entire applicator tip may be driven with force 1655against the tissue, as shown in FIGS. 16H-161, first to contact thetissue, then to continue to apply force 1656, so that the distal-facinginsulator of the applicator tip 1603 pushes against the surface of thetissue to be treated; in this example, the tissue deforms slightly tomatch the applicator. The distal-facing insulating end of the electrodepartition may not be soft (e.g., semi-compliant) or it may be compliant.Thus, the electrode partitions described herein may include a softdistal cover or may just be an insulating material (that is notcompliant). Distally-directed force 1656, as shown in FIG. 16J, drivesthe electrodes 1605 into the tissue while pushing and retracting theelectrode partition proximally, allowing the electrodes to penetrate thetissue and the insulator to press against the tissue and insulatebetween the electrodes. Once the electrodes have been positioned (inthis example in FIG. 16K to a maximum depth allowed, for example, by theretracted electrode partition), as shown in FIG. 16K, power, includingin particular nsPEF therapy, may be applied. Thereafter, the applicatortip may be withdrawn, as shown in FIG. 16L by arrow 1657; anytherapeutic effect on the treatment site 1693 may result eitherimmediately or within a reasonably short time period.

FIGS. 17A-17D illustrate another example of a treatment tip device fordelivery of electrical therapy. The device includes a treatment tiphousing 1701 and an electrode partition 1703 that extends from a distalend of the treatment tip housing. The electrode partition 1703 includesone or more lateral cut-outs or window openings 1709. The lateral sidesof a first set of electrodes 1705 and a second set of electrodes 1707are visible through these lateral cut-outs or window openings in anun-deployed or pre-treatment configuration. Thus, the device includes aplurality of treatment electrodes; in this example, the treatmentelectrodes are needle electrodes. The treatment electrodes may include afirst one or more treatment electrodes (e.g., four are shown on the leftin FIG. 17A), and a second one or more treatment electrodes (e.g., fourare shown on the right in FIG. 17A) separated from the first one or moretreatment electrodes by the electrode partition. The electrode partitionin this example is similar to the electrode housing of FIGS. 3A, 4A-B.The electrode partition may be formed of an insulating material(entirely or at least at the distal end of the partition. In particular,the region between and/or adjacent to the treatment electrodes may beformed of an electrically insulating material. The distal end face 1711of the electrode partition 1703 may be relatively soft (e.g., may have adurometer of 60 or less on the Shore A hardness scale). In FIG. 17A, thecut-outs or window openings(s) 1709 on the lateral sides of theelectrode partition extend to the distal end face 1711. In somevariations the window openings may not extend all the way to the distalend face, for example, such that the tips of the electrodes are notvisible in the window openings in the un-deployed configuration but maybe beneath a cover as described above. In FIG. 17A the lateral windowopenings extend only partially along the sides of the electrodepartition; in some variation the lateral window openings may extend moreor less along the sides of the electrode partition. In some variationsthe lateral side is open (e.g., the cut-out or window opening extendsdown the entire side of the electrode partition, as shown in FIGS.18A-18B). In FIGS. 17A and 17B, by example, the two lateral cut-outsshow the distal end regions of the first one or more electrodes 1705 andthe second one or more electrodes 1707. In some variations a smallercut-out(s) allowing visualization of subsets (or individual) electrodesmay be included; in some variations each electrode may be visiblethrough a lateral window.

In FIG. 17A, the device is shown with the electrode partition in anun-deployed configuration in which the distal ends of the first one ormore treatment electrodes are separated from the distal ends of thesecond one or more treatment electrodes by the electrode partition. FIG.17B shows the device in a deployed configuration in which the pluralityof treatment electrodes 1705, 1707 extend distally beyond the electrodepartition (e.g., distally beyond the distal end face 1711 of theelectrode partition). As described above, the electrode partition andtreatment electrodes may be configured to move relative to each other toconvert between the un-deployed and the deployed configurations. InFIGS. 17A and 17B the electrode partition retracts at least partially(e.g., about 40%) into the treatment tip housing. As described above, abias within the treatment tip housing may exert a force (e.g., a biasreturn force) to oppose conversion from the un-deployed to the deployedconfiguration or from the deployed to un-deployed configuration; in thisexample, a force (arrow 1720) may drive the electrode partition 1703into the treatment tip housing 1701 when the force is greater than thethreshold force.

FIGS. 17C and 17D show side views of the device of FIGS. 17A and 17Bwith the electrode partition 1703 in the un-deployed (FIG. 17C) anddeployed (FIG. 17D) configurations, respectively. As described above,the treatment tip housing 1701 may include a mechanical connector 1721(shown by example as a snap or latch) that couples the retractabletreatment tip to a handle. The retractable treatment tip also includestwo or more electrical connectors (not visible in FIGS. 17A-17D) forcoupling the electrodes 1705, 1707 to the controller and/or powersupply.

FIGS. 18A-18B show another example of a treatment tip device fordelivery of electrical therapy in which the electrode partition 1803 isretractable into the treatment tip housing 1801 (shown in FIG. 18B). Inthis example the electrode partition does not enclose the electrodeseven partially, but extends between the first set (e.g., of one or moreelectrodes) 1805 and the second set (e.g., of one or more electrodes)1807, and may insulate them from each other and prevent or limit arcing.In this example, the lateral windows or cut outs extend completely alongthe length of the electrode partition into the treatment tip housing, orthese lateral regions may be missing entirely, so that the first andsecond sets of electrodes extend on either sides of the electrodepartition. In some variations the electrode partition may partiallyenclose the first and second sets of electrodes, e.g., curving around(and in some variations between) them. For example, the electrodepartition may have an I-shaped cross-section, in which the top andbottom of the “I” shape extend partially around the sides of the firstand second sets of electrodes, leaving the lateral, outward-facing sidesopen.

In any of the exemplary electrode partitions shown in FIGS. 17A-18B, thelateral openings (e.g., lateral windows), may be referred to as lateralcut-out regions from the electrode partition and may allow visualizationof the electrodes even in the un-deployed configurations, so that theelectrodes may be visualized before or during deployment. This may aidthe user in targeting a tissue (e.g., a lesion) to be treated, includingpositioning the target tissue between the electrodes (e.g., in betweentwo rows of needles for the variations shown in FIGS. 17A-18B). Thisconfiguration may also allow the user to verify the orientation of theelectrodes.

FIG. 19 illustrates a flowchart of an example of a general method oftreatment. In FIG. 19, the method is a method of, e.g., applyinghigh-voltage nanosecond pulse electrical therapy to treat a subject. Themethod may include, as a preliminary step 1901, initially positioning aretractable treatment tip against a subject's tissue. In step 1903, aplurality of electrodes of a retractable treatment tip are inserted intothe tissue (out and past the distal face of the electrode partition)while the electrode partition is retracted into the tip housing. In someembodiments the treatment tip device may be pushed against the subject'stissue with a force that is greater than a threshold force necessary toretract the electrode partition proximally relative to the plurality ofelectrodes while penetrating the tissue with the plurality ofelectrodes. When bias is present, the applied driving force may overcomethe bias (the threshold force). The electrode partition (e.g., housing)may be driven against the tissue to help electrically isolate theplurality of electrodes from each other. Alternatively or additionally,the tissue-penetrating (e.g., needle) electrodes may be deployed byreleasing a bias (or by applying a force greater than the thresholdforce set by the bias) to drive the electrode distally relative to thedistal face of the electrode partition, so that they penetrate thetissue and simultaneously drive the distal face of the electrodepartition against the tissue.

In general, the retractable treatment tip may be any of the applicatortips (treatment tips) described herein, particularly those including anelectrode partition (or electrode housing) extending from a distal endof a treatment tip housing. The retractable treatment tip may alsocomprise a bias, for example, a bias holding and in some variationsdriving the electrode partition distally with a bias return force, and aplurality of treatment electrodes at least partially within theelectrode partition. The retractable treatment tip may also comprise aninsulator, for example, a distal insulating cover covering theelectrodes within the electrode partition. In step 1905 (which mayoccur, for example, simultaneously with the step 1903), the plurality ofelectrodes are insulated against the tissue. In some embodiments, theelectrodes may be insulated with the use of an insulator (e.g.,insulating cover, or insulating material), or with the use of one ormore vacuum ports, or both.

Once the treatment electrodes are inserted into the tissue (e.g., skin)to the desired depth, including fully deployed as limited by the fullretraction position of the electrode partition, in step 1907 a therapy,such as electrical energy therapy, may be applied to the tissue. Forexample, high-voltage nanosecond electrical pulses may be applied to thetissue from the plurality of electrodes. As mentioned above, the step ofapplying energy may be done without the need for any additionalinsulator or insulating material (e.g., gel) between the applicator tipand the tissue. Upon completion of the application of energy, in step1909 the tip may be removed from the tissue (e.g., by withdrawing theapplicator tip). If there are additional regions to be treated, theapplicator tip may be removed to the new location, typically on the sameperson, or they may be completely removed.

Also described herein are hooks, latches, and holsters for the reusablecomponent (e.g., handle such as a gun or other form factor that may beused to hold the applicator (with or without the treatment tipsdescribed herein). For example, FIGS. 20A and 20B illustrate thetemporary attachment of an applicator gun for use with the applicatortips described herein. In this example the reusable applicator issecured over a lip or edge by an attachment site on the applicator. FIG.20B shows the apparatus of FIG. 20A coupled to a lip or edge.

In some variations an additional hook or tool, such as the hook shown inFIG. 21A, may be used as an intermediate between the reusable handle andan edge or other exposed outer surface, e.g., or an operating table orthe like. A longer version of the hook may be used as a holster for thegun applicator (or other shapes/configurations of the applicator tip andapplicator housing, as shown in FIGS. 21B and 21C. In FIG. 21B, the hook2109 is attached over a lip of a surgical tray or cart, including a cartholding the rest of the applicator system. In FIG. 21C, the hook 2109 isshown attached onto a tray or table edge and the applicator handle 2189is held within the hook.

Any of the methods (including user interfaces) described herein may beimplemented as software, hardware or firmware, and may be described as anon-transitory computer-readable storage medium storing a set ofinstructions capable of being executed by a processor (e.g., computer,tablet, smartphone, etc.), that when executed by the processor causesthe processor to perform any of the steps, including but not limited to:displaying, communicating with the user, analyzing, modifying parameters(including timing, frequency, intensity, etc.), determining, alerting,or the like.

When a feature or element is herein referred to as being “on” anotherfeature or element, it can be directly on the other feature or elementor intervening features and/or elements may also be present. Incontrast, when a feature or element is referred to as being “directlyon” another feature or element, there are no intervening features orelements present. It will also be understood that, when a feature orelement is referred to as being “connected”, “attached” or “coupled” toanother feature or element, it can be directly connected, attached orcoupled to the other feature or element or intervening features orelements may be present. In contrast, when a feature or element isreferred to as being “directly connected”, “directly attached” or“directly coupled” to another feature or element, there are nointervening features or elements present. Although described or shownwith respect to one embodiment, the features and elements so describedor shown can apply to other embodiments. It will also be appreciated bythose of skill in the art that references to a structure or feature thatis disposed “adjacent” another feature may have portions that overlap orunderlie the adjacent feature.

Terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting. For example, asused herein, the singular forms “a”, “an” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. As used herein, the term “and/or” includes any and allcombinations of one or more of the associated listed items and may beabbreviated as “/”.

Spatially relative terms, such as “under”, “below”, “lower”, “over”,“upper” and the like, may be used herein for ease of description todescribe one element or feature's relationship to another element(s) orfeature(s) as illustrated in the figures. It will be understood that thespatially relative terms are intended to encompass differentorientations of the device in use or operation in addition to theorientation depicted in the figures. For example, if a device in thefigures is inverted, elements described as “under” or “beneath” otherelements or features would then be oriented “over” the other elements orfeatures. Thus, the exemplary term “under” can encompass both anorientation of over and under. The device may be otherwise oriented(rotated 90 degrees or at other orientations) and the spatially relativedescriptors used herein interpreted accordingly. Similarly, the terms“upwardly”, “downwardly”, “vertical”, “horizontal” and the like are usedherein for the purpose of explanation only unless specifically indicatedotherwise.

Although the terms “first” and “second” may be used herein to describevarious features/elements (including steps), these features/elementsshould not be limited by these terms, unless the context indicatesotherwise. These terms may be used to distinguish one feature/elementfrom another feature/element. Thus, a first feature/element discussedbelow could be termed a second feature/element, and similarly, a secondfeature/element discussed below could be termed a first feature/elementwithout departing from the teachings of the present disclosure.

Throughout this specification and the claims which follow, unless thecontext requires otherwise, the word “comprise”, and variations such as“comprises” and “comprising” means various components can be co-jointlyemployed in the methods and articles (e.g., compositions and apparatusesincluding device and methods). For example, the term “comprising” willbe understood to imply the inclusion of any stated elements or steps butnot the exclusion of any other elements or steps.

In general, any of the apparatuses and methods described herein shouldbe understood to be inclusive, but all or a sub-set of the componentsand/or steps may alternatively be exclusive, and may be expressed as“consisting of” or alternatively “consisting essentially of” the variouscomponents, steps, sub-components or sub-steps.

As used herein in the specification and claims, including as used in theexamples and unless otherwise expressly specified, all numbers may beread as if prefaced by the word “about” or “approximately,” even if theterm does not expressly appear. The phrase “about” or “approximately”may be used when describing magnitude and/or position to indicate thatthe value and/or position described is within a reasonable expectedrange of values and/or positions. For example, a numeric value may havea value that is +/−0.1% of the stated value (or range of values), +/−1%of the stated value (or range of values), +/−2% of the stated value (orrange of values), +/−5% of the stated value (or range of values), +/−10%of the stated value (or range of values), etc. Any numerical valuesgiven herein should also be understood to include about or approximatelythat value, unless the context indicates otherwise. For example, if thevalue “10” is disclosed, then “about 10” is also disclosed. Anynumerical range recited herein is intended to include all sub-rangessubsumed therein. It is also understood that when a value is disclosedthat “less than or equal to” the value, “greater than or equal to thevalue” and possible ranges between values are also disclosed, asappropriately understood by the skilled artisan. For example, if thevalue “X” is disclosed the “less than or equal to X” as well as “greaterthan or equal to X” (e.g., where X is a numerical value) is alsodisclosed. It is also understood that the throughout the application,data is provided in a number of different formats, and that this data,represents endpoints and starting points, and ranges for any combinationof the data points. For example, if a particular data point “10” and aparticular data point “15” are disclosed, it is understood that greaterthan, greater than or equal to, less than, less than or equal to, andequal to 10 and 15 are considered disclosed as well as between 10 and15. It is also understood that each unit between two particular unitsare also disclosed. For example, if 10 and 15 are disclosed, then 11,12, 13, and 14 are also disclosed.

Although various illustrative embodiments are described above, any of anumber of changes may be made to various embodiments without departingfrom the scope of the disclosure as described by the claims. Forexample, the order in which various described method steps are performedmay often be changed in alternative embodiments, and in otheralternative embodiments one or more method steps may be skippedaltogether. Optional features of various device and system embodimentsmay be included in some embodiments and not in others. Therefore, theforegoing description is provided primarily for exemplary purposes andshould not be interpreted to limit the scope of the invention as it isset forth in the claims.

The examples and illustrations included herein show, by way ofillustration and not of limitation, specific embodiments in which thesubject matter may be practiced. As mentioned, other embodiments may beutilized and derived there from, such that structural and logicalsubstitutions and changes may be made without departing from the scopeof this disclosure. Such embodiments of the inventive subject matter maybe referred to herein individually or collectively by the term“invention” merely for convenience and without intending to voluntarilylimit the scope of this application to any single invention or inventiveconcept, if more than one is, in fact, disclosed. Thus, althoughspecific embodiments have been illustrated and described herein, anyarrangement calculated to achieve the same purpose may be substitutedfor the specific embodiments shown. This disclosure is intended to coverany and all adaptations or variations of various embodiments.Combinations of the above embodiments, and other embodiments notspecifically described herein, will be apparent to those of skill in theart upon reviewing the above description.

What is claimed is:
 1. A method of treating a subject, the methodcomprising: placing an electrode housing of a treatment applicatoradjacent to the subject's tissue, wherein the treatment applicator is inan un-deployed configuration, in which distal ends of a plurality oftreatment electrodes do not extend beyond a soft, electricallyinsulating distal end of the electrode housing; driving the treatmentapplicator against the subject's tissue to convert the treatmentapplicator to a deployed configuration in which the electrode housing isretracted proximally relative to the plurality of treatment electrodesand the plurality of treatment electrodes extends beyond the soft,electrically insulating distal end of the electrode housing and into thesubject's tissue; and holding the soft, electrically insulating distalend of the electrode housing against the subject's tissue to preventarcing between the plurality of treatment electrodes when energy isapplied to the subject's tissue from the plurality of treatmentelectrodes.
 2. The method of claim 1, further comprising applying energyto the subject's tissue from the plurality of treatment electrodes. 3.The method of claim 2, wherein applying energy comprises applying asub-microsecond pulsed electric field.
 4. The method of claim 1, whereinplacing the electrode housing of a treatment applicator adjacent to thesubject's tissue comprises positioning the treatment applicator againstsubject's skin.
 5. The method of claim 1, further comprising releasing arelease lock to allow the electrode housing to be retracted proximallyinto a treatment tip housing of the treatment applicator.
 6. The methodof claim 1, wherein driving the treatment applicator against thesubject's tissue comprises driving the treatment applicator with a forcethat is greater than a threshold force necessary to overcome a biasholding the electrode housing extended from a treatment tip housing ofthe treatment applicator in the un-deployed configuration.
 7. The methodof claim 1, wherein placing the electrode housing of the treatmentapplicator adjacent to the subject's tissue comprises placing theelectrode housing adjacent to one or more of: a malignant tumor orlesion of any stage and grade, a benign tumor or lesion, and apre-cancerous tumor or lesion.
 8. The method of claim 1, furthercomprising applying sub-microsecond electric pulses from the pluralityof treatment electrodes to treat at least one of the following:digestive and gastrointestinal cancers, colorectal cancer,gastrointestinal stromal tumors, gastrointestinal carcinoid tumors,colon cancer, rectal cancer, anal cancer, bile duct cancer, smallintestine cancer, esophageal cancer; breast cancer, lung cancer,gallbladder cancer, liver cancer, pancreatic cancer, appendix cancer,prostate cancer, ovarian cancer, renal cell carcinoma, cancer of thecentral nervous system, skin cancer, lymphomas, gliomas,choriocarcinomas, head and neck cancers, osteogenic sarcomas, bloodcancer, and Kaposi's sarcoma.
 9. The method of claim 1, furthercomprising applying sub-microsecond electric pulses to from theplurality of treatment electrodes to treat at least one of: skinlesions, aging skin, skin tumors, acne, seborrheic keratosis, keloids,scars, molluscum contagiosum, acrochordon, psoriasis, papilloma, humanpapilloma virus (HPV), melanoma, melasma, sebaceous hyperplasia (SH),syringoma, congenital capillary malformation (port-wine stains),congenital nevi, actinic keratosis, dermatosis papulosa nigra,angiofibroma, cherry angioma, warts, molluscum angioma, necrobiosislipoidica (NBL), melisma, lipoma epidermal/sebaceous cyst, and basalcell carcinoma.
 10. The method of claim 1, further comprising applyingsub-microsecond electric pulses to from the plurality of treatmentelectrodes to treat at least one of the following cosmetic treatments:tattoo removal, hair follicle destruction, aging skin, scar/keloidsreduction, fat reduction, and wrinkle reduction.
 11. The method of claim1, further comprising setting a length of the plurality of treatmentelectrodes prior to driving the soft, electrically insulating distal endof the electrode housing against the subject's tissue.
 12. The method ofclaim 1, wherein driving the treatment applicator against the subject'stissue comprises penetrating the soft, electrically insulating distalend of the electrode housing with the plurality of treatment electrodes.13. The method of claim 1, wherein a material of the soft, electricallyinsulating distal end has a durometer of 60 or less on the Shore Ahardness scale against the subject's tissue.
 14. The method of claim 1,wherein the soft, electrically insulating distal end of the electrodehousing extends at least partially down a side of the electrode housing.15. The method of claim 1, wherein the soft, electrically insulatingdistal end of the electrode housing comprises an electrically insulatingcover.
 16. The method of claim 1, wherein the soft, electricallyinsulating distal end comprises one or more of: silicon, santoprene, orother TPE (Thermoplastic Elastomer) materials.
 17. The method of claim1, further comprising adjusting a distal-to-proximal length of theplurality of treatment electrodes.
 18. The method of claim 1, whereinthe plurality of treatment electrodes comprises needle electrodes. 19.The method of claim 1, further comprising releasably coupling thetreatment applicator to a handle.
 20. A method of treating a subject,the method comprising: positioning a treatment tip against the subject'stissue, wherein the treatment tip comprises a bias and an electrodehousing extending from a distal end of a treatment tip housing, theelectrode housing having a soft, electrically insulting distal end and aplurality of needle electrodes within the electrode housing, furtherwherein the treatment tip is in an un-deployed configuration in whichthe electrode housing extends over the plurlaity of needle electrodes;deploying the treatment tip by driving the electrode housing against thesubject's tissue so that the electrode housing is retracted into thetreatment tip housing against the bias while the plurality of needleelectrodes are inserted into the subject's tissue, wherein the soft,electrically insulating distal end is applied against the subject'stissue to electrically isolate the plurality of needle electrodes andprevent or reduce arcing; and applying energy to the subject's tissuefrom the plurality of needle electrodes.
 21. A method treating asubject, the method comprising: positioning a treatment tip adjacent tothe subject's tissue, wherein the treatment tip comprises an electrodehousing extending from a distal end of a treatment tip housing and abias applying a bias force to hold the electrode housing extended fromthe treatment tip housing and over a plurality of needle electrodeswithin the electrode housing, the electrode housing including a soft,electrically insulating distal end having a durometer of 60 or less onthe Shore A hardness scale; pushing the treatment tip against thesubject's tissue with a force that is greater than the bias force todrive the electrode housing proximally relative to the plurality ofneedle electrodes while penetrating the subject's tissue with theplurality of needle electrodes; and applying nanosecond electricalpulses to the subject's tissue from the plurality of needle electrodeswhile holding the soft, electrically insulating distal end against thesubject's tissue to electrically isolate the plurality of needleelectrodes and prevent or reduce arcing.